ASCO Guidelines

Dr. Bradley Hunter, MD, MPH and Ms. Amy Evers, BSN, RN, OCN, MBA join us on the latest episode of the ASCO Guidelines Podcast to share key points and insights on the updated ASCO-ONS antineoplastic therapy administration safety standards for adult and pediatric oncology standards. They highlight key updates across the four standards domains: (1) creating a safe environment, (2) patient consent and patient education, (3) ordering, preparing, dispensing, and administering oral and parenteral antineoplastic therapies in a health care facility, organization, or in the home, and (4) monitoring during and after antineoplastic therapy is administered, including adherence, toxicity, and complications. They also comment on the importance of these standards to provide a framework for optimal safe and effective care for all patients. Read the standards, “Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards” at www.asco.org/standards. TRANSCRIPT These standards, clinical tools, and resources are available at www.asco.org/standards. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the JCO Oncology Practice, https://ascopubs.org/doi/10.1200/OP.24.00216 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Bradley Hunter from Intermountain Health and Amy Evers from the University of Pennsylvania, authors on “Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: American Society of Clinical Oncology – Oncology Nursing Society Standards.” Thank you both for being here. Dr. Bradley Hunter: Yeah, thanks. Good to be with you. Amy Evers: Thank you. Brittany Harvey: Now, before we discuss these standards, I'd like to note that ASCO takes great care in the development of its guidance products and ensuring that the ASCO Conflict of Interest Policy is followed for all standards. The disclosures of potential conflicts of interest for the expert panel are available online with the publication of the standards in the JCO Oncology Practice, which is linked in the show notes.  So then to start us off, Dr. Hunter, what prompted an update to the ASCO-ONS standards? And what is the scope of this update? Dr. Bradley Hunter: The last guidelines were published in 2016. And just thinking about in the world of oncology, so much has changed since that time. There are a lot of therapies that have become commonplace now that were really not used too much before, including oral genomically determined targeted therapies, immunomodulatory agents, CAR T cell therapy, bispecific antibodies, etc. So there's really been a need to just talk about how do we navigate those therapies and how do we create systems of care in which they are delivered safely. Additionally, the sites of care have changed. I think all of us, eight years ago, wouldn’t have imagined a global pandemic, and how that would have changed the way that we needed to deliver oncology care. So there's been a huge influx of telehealth, including tele-oncology centers, where the oncologist and the patient may never even meet face to face, but just by video. And so it relies on a team approach for that sort of an outreach setting. Intermountain Health spans seven states, there are so many sites like this that we have and I know that we are not unique. This is an issue and a global thing now. Additionally, patients are even getting chemo in their own homes, so that has changed and we need to figure out how to address that so that everyone could be able to have that site of care so they can get there and they can get their therapy in a safe manner.  So, these varied care settings present a challenge to us as oncology providers to ensure that a standard of quality of care is maintained, and that the therapies can be given to patients no matter where they live and that we maximize benefit while minimizing risk to the patient. So I mean, just thinking where we are now, I can't imagine where we're going to be eight years from now or the next time these guidelines are updated. Brittany Harvey: Absolutely. Thank you for setting the stage and the impetus for this update. It sounds like a lot has changed in the last few years to impact these standards.  So then I'd like to review the key points of the standards and the key updates for our listeners. There are four domains of standards. Starting with domain one, Amy, what are the key points of the standards for creating a safe environment for all routes of antineoplastic therapy? Amy Evers: So domain one is all about who can write chemotherapy orders, who can prepare chemotherapy and then who can administer that chemotherapy and then what their competencies are both initial and then ongoing. So looking at the existing standards, we did end up making a few updates mainly on how providers discuss and document pregnancy status and fertility preservation with patients. And I think this is really timely given that we're seeing a big uptick in younger patients that are being diagnosed with cancers that were typically considered “old person diseases”. And I think we can and we should do better in ensuring that patients who want to preserve their ability to have a family one day can do so before they start treatment.  The update also included the addition of an assessment for social determinants of health, calling out financial and logistical constraints that patients may face as part of their cancer journey, which I think is extremely important making sure that we have equitable access to care regardless of a patient's background, their financial status, everybody's receiving the highest quality of care they can in their community.  And the last change that we made was to highlight an accurate measurement of height and weight using metric units, which is important when we're calculating the doses of drugs for some of these very high risk medications.  Brittany Harvey: Excellent. Thank you for reviewing those important points for our listeners.  So following those standards, for domain two, Dr. Hunter, what are the key standards for patient consent and patient education? Dr. Bradley Hunter: In domain two, we’re really seeking to figure out what policies around treatment planning, patient consent and patient's education are shown to result in fewer medical errors and reduce preventable harm? But one of the big things we've found is having a really detailed understanding of exactly what a patient is taking in terms of medications, including over the counters and supplements and herbal remedies, really helps reduce medical errors. You know, some of the research and literature we came across suggest that upwards of 80% of the time when you see a patient's medication there are discrepancies between what's on that list and what patients are actually taking. So being able to sit down as part of a consent discussion and ongoing care and talk about everything that a patient's taking is really important.  My background, I am a bone marrow transplant, stem cell transplant and cellular therapist. Just this last weekend I was on the inpatient service and a patient had brought in food from home which we completely are supportive of. The patient brought in a bunch of superfood shakes that she had bought at Costco and then some CBD tea and she asked us if it was okay if she could take those. And as we reviewed them and what was in all of those shakes and then what was in the CBD tea, there were major interactions between those supplements or those herbal remedies, and then what was in the medications we were giving in the hospital, so it was important. And she told us - it wasn't like I sat down and and was the shining example here, but it was helpful that we were able to take her global picture of what she was taking from a medication standpoint and be able to make sure that we were treating her in a safe manner and making sure that we weren't inadvertently causing harm.  So, those are some of the things that we talked about. So, at every patient visit, and especially the first time you meet a patient you’re going to start therapy to be able to go over all of the different substances that patients are taking to make sure that they're safe.  Brittany Harvey: Thank you so much for reviewing those key standards and key updates and that example of how important it is to review all of medications and herbal supplements that patients are taking to ensure safe care for our patients.  So then following that, Amy, for domain three, what are the key points regarding ordering, preparing, dispensing and administering oral and parenteral antineoplastic therapy in a healthcare facility organization or in the home? Amy Evers: So, domain three, actually, it was the domain that had probably the biggest discussion and fruitful debate between the panel members, but I think that we had some really great discussions and I think we had brought some really good changes and updates to the standards here. So domain three is where all of the verification standards live. So this is for practices who would either have been through the QOPI certification process or have been QOPI certified. This is where the surveyor actually will observe in real time how the clinical orders are reviewed by staff, how the drugs are prepared by pharmacy, and then how the drugs are checked one final time at the chair side or bedside immediately prior to administration.  So as I mentioned earlier, antineoplastic therapies are being given more frequently in the home or in settings where there may not be two clinical staff members present. In this post-COVID world, we're finding patients can be treated safely in the home, but the standards didn't really reflect kind of these changes in where patients are receiving treatment. And often, more and more practices are relying on technology to supplement the verification process both either in the pharmacy setting where there may be a centralized pharmacist verifying the drug mixing process for multiple sites, or in the actual home setting where a nurse can connect virtually with another clinician to verify a drug immediately or administration. So the standards were updated to include these workflows. And I think it's becoming more and more commonplace, but how do we do this in a safe and effective way where we're ensuring that all of these same safe handling processes are completed, regardless of where the patient may be seeking treatment?  So previous versions of the standards had three verifications. The first was before the actual preparation of the drug that someone other than the provider who wrote the order is verifying the order for all of the correct elements. The second verification is what usually happens in the pharmacy, upon preparation, what's being checked by the pharmacist or pharmacy technician who's preparing the drug. And then a third verification is done at, generally, the chair side where they're doing one final check of the orders to the drug to the patient.  So with this update, we actually broke out that third verification into a fourth verification. So the third verification is that check with the drug in the order by the administering and then a second verifier. And then the fourth verification is actually the one where the patient’s involved in the verification. So there are two clinicians making that final double check with the patient immediately upon preparation, which I think is important and is reflective of this change that we're seeing more drugs being administered in the home setting. The chair side or bedside final verification was also expanded to include a visual inspection of the administration tubing, this is sometimes referred to as tracing the lines, which ensures that the drug is being accurately infused, that there aren't any loose connections, that the clamps are open etc. And I think this is something that most nurses do in their normal clinical practice, but I think adding this as an actual check in the verification process, is really important. And I know personally, I was really happy to see this added in as a formal check. Dr. Bradley Hunter: Yes, thanks, Amy. One other new standard within domain three is regarding immunomodulatory or immune effector cell therapies that have the risk of cytokine release syndrome and how we build a framework to try to mitigate those toxicities. We really wanted to try to make a set of standards that would apply whether or not you’re at a coronary care center, like Penn or whether you were at a center, like within Intermountain Health, it's a small rural outreach center that you're trying to be able to get patients to care. So really, the main thing within dealing with therapies that have the risk of cytokine release syndrome is really just building a framework that there's a management policy that's present from the institution, and that it's up to date, it's following what we know will work for these therapies in order to mitigate their toxicity, and then also making sure that adequate antidote therapy, whether for example, for cytokine release syndrome, it could be tocilizumab or anakinra or other therapies, and that order sets are present to be able to follow along with the policy guidelines to guide clinicians wherever they are practicing to help mitigate cytokine release syndrome, neurologic toxicity, ICANS, or other sorts of therapies that are associated with these novel agents.  Brittany Harvey: So for or the last domain, domain four, what are the key points for monitoring during and after antineoplastic therapy is administered, including adherence, toxicity, and complications? Amy Evers: So domain four is pretty straightforward. It discusses the importance of assessing adherence and toxicities related to antineoplastic treatments. There wasn’t a whole lot of updates here. We did include having emerging treatment plans or equipment in the home and the healthcare setting. But what I really think is important and we need to underscore both with patients and clinicians, particularly as we've seen this rise in oral chemotherapy agents, is that a lot of times patients forget that this is the same chemotherapy that they're getting in the infusion suite. They're just taking it in a pill form. And I think patients forget that their adherence is just as important in taking that pill regularly and as prescribed. Financial toxicity is a real problem for most of our patients. Some of these drugs cost hundreds if not thousands of dollars for one treatment plan. As clinicians we've all heard stories of these patients who try to extend their prescription so they'll take a pill every other day instead of daily as prescribed, which really doesn't let the drug do what it's supposed to do. So I think when we talk about adherence, it's not just asking a patient whether they've taken their drug, it's about whether or not oral therapy is even appropriate for that particular patient. Do they have memory problems? Do they have metastatic disease to the brain where they may not be able to follow a complicated oral regimen? Do they have arthritis where opening a pill container is difficult? So having these conversations before a drug is even prescribed and making sure that it's the right route of administration for a patient is just as important as ensuring that they're maintaining their adherence to that drug.  And oftentimes, the toxicities of these oral drugs are worse than what's actually being administered in some of the infusion clinics, and so making sure that we're checking in on these patients regularly to ensure that they're not having any toxicities that aren't being managed appropriately. Or if there may be toxicities that would require a dose reduction, or perhaps switching to a different drug entirely. So, even though it's a pretty simple and straightforward domain, I think it's really important that we're educating our clinicians and our patients about the importance of adherence.  Dr. Bradley Hunter: I completely agree with what Amy said. She said it so well. I just want to echo back a couple of things that she said. Historically, we use the word non-compliant, which I think kind of sounds terrible to describe the patient's adherence to medication. I think part of this domain is recognizing that there is an entire environment that has to do with the patient that influences the way they're able to take their medication whether that's financial toxicity; we were talking to two people in our clinic who are professional financial toxicologists, and their entire job description is to help people get drugs for less so that they can actually take the side effects. If a patient feels terrible at that time, they’re not going to take it. So, understanding these barriers and really understanding the patient's entire picture, when you're figuring out how is the treatment plan going to match up with their reality, I think is super important.  When it comes to site of care, we just want to make sure also that whether you're getting chemo at home or you’re getting chemo in the clinic down the street, or in a coronary care center, that there is a policy in place to respond to an emergency, but also the equipment available in all of those sites of care that you can respond. And that's another aspect that we wanted to make sure we hit in the domain as there's been so many changes in how patients get care in the last eight years. Brittany Harvey: Absolutely. Recognizing the barriers and factors that impact the ability of an individual to receive the right therapy is crucial. And I want to thank you both for reviewing all of the standards and updates through all four domains.  So then following that, in your view, how will these updated standards impact clinicians? Dr. Bradley Hunter: It's our hope that these standards will guide the development of treatment infrastructure and help clinicians avoid error prone environments. We hope they're going to guide training efforts and that they will help clinicians ensure that they have relevant and accurate information about their patients and are able to respond appropriately when emergencies or even urgencies arise. Because of COVID, there's been such high staff turnover. And in the midst of all of this change, it's difficult to maintain a culture of safety when you've lost a lot of institutional knowledge of how to deal with that. And so, really trying to help bring people together again to have an infrastructure in place that makes training as seamless as possible and deal with the historical high staff turnover we’ve had.  So we're again, hopeful that we're helping to create a framework that cancer centers, treatment centers can use, whether they are a coronary care center in a large academic space, or whether they're in a rural tele-oncology space to be able to use the standards to create a space and a place and experience for cancer patients in which they’re kept safe and we’re maximizing the benefit of their chemotherapy, their antineoplastic agents, and also minimizing the risk just to optimize benefits for the patient.  Brittany Harvey: Definitely. Those are key points to provide a framework for clinicians.  So then along those same lines, finally, what does this update mean for patients receiving antineoplastic therapy?  Amy Evers: So while these standards are not necessarily patient facing, what I hope that this update will do, or actually not do, is that a patient shouldn't recognize any change in how they are cared for, regardless of what setting that they're receiving treatment. So whether it's at home, whether it's an ambulatory infusion center or in the hospital, they're still going to receive that same level of high quality care while they're receiving treatment. And I think that that's the most important thing that they should take away from this. Brittany Harvey: Absolutely.  So I want to thank you both so much for all of your work on these standards to ensure patients receive optimal safe and effective care. And I want to thank you both so much for your time today.  Amy Evers: Thank you so much.   Dr. Bradley Hunter: Yeah, thank you. It’s really great to talk about this stuff.  Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the complete standards go to www.asco.org/standards. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

Dr. Rachel Freedman and Dr. Sharon Giordano share the latest rapid guideline update from ASCO on the adjuvant use of the CDK4/6 inhibitors abemaciclib and ribociclib in patients with stage II and III breast cancer. They share details on the impetus for the update, supporting evidence, and considerations of benefits and harms for individuals. Additionally, Drs. Freedman and Giordano discuss what these options mean for clinicians and patients, and outstanding questions regarding optimal adjuvant chemotherapy and targeted therapy for patients with early breast cancer. Read the full rapid update, “Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer – CDK4/6 Inhibitors: ASCO Rapid Guideline Update” at www.asco.org/breast-cancer-guidelines." TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00886  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Rachel Freedman from Dana Farber Cancer Institute and Dr. Sharon Giordano from MD Anderson Cancer Center, co-chairs on “Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer – CDK 4/6 Inhibitors: ASCO Rapid Guideline Update.” Thank you for being here, Dr. Freedman and Dr. Giordano. Dr. Rachel Freedman: Hi. It's great to be here, thank you. Dr. Sharon Giordano: Yeah, thank you for having us. Brittany Harvey: Great. Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Freedman and Dr. Giordano, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content here. First, Dr. Freedman, what prompted this update to the “Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer Guideline”, which was previously updated in 2021? Dr. Rachel Freedman: Yeah, at that time, we published guidelines which were part of an amendment to the previously published 2020 early breast cancer guidelines to include consideration of adjuvant CDK4/6 inhibitor use, because the first data for adjuvant abemaciclib became available from the monarchE trial, and because the FDA had acted to grant approval for the use of abemaciclib in those with node positive disease and a Ki-67 score of at least 20%. Our recommendation at that time was to apply abemaciclib in the greater context of the intention-to-treat population included on the monarchE study. But since that time, the FDA in 2023 expanded its approval for adjuvant abemaciclib for a broader population, removing that Ki-67 requirement that was a part of their initial approval. With this change, the recently published longer term data from the monarchE study and the recently published data from the NATALEE trial and adjuvant ribociclib study, we felt that it was time to update our guidelines to be more relevant to the most current data available. Brittany Harvey: I appreciate you providing that background information on the impetus for this latest update. So then, Dr. Giordano, based on this new data, what are the updated recommendations in the latest version of this guideline? Dr. Sharon Giordano: So we really have two updated recommendations and then two qualifying statements that go with the new recommendations. So the first recommendation focuses on the use of adjuvant abemaciclib, which, as Rachel noted, was included in our previous guideline. So this recommendation is that abemaciclib for two years plus endocrine therapy for five or more years may be offered to patients who meet the criteria of the intent-to-treat analysis in the monarchE study. These are patients with resected, hormone receptor-positive, HER2-negative, node-positive breast cancer at high risk of recurrence. The way the study defined the high risk of recurrence was having either four or more lymph nodes involved, axillary lymph nodes involved, or having one to three lymph nodes, plus other high risk features, which included having a grade three tumor the size of 5 cm or greater, or having a Ki-67 of more than 20%. And so, although the FDA has dropped the requirement for the Ki-67 testing, and the language is quite broad now, the panel recommends the use of abemaciclib, really in that subgroup of patients that would have been eligible for the original monarchE study. That's the first recommendation, kind of a long one, but that was the update. The second recommendation focuses on the use of adjuvant ribociclib, and this is based on the data from the phase three NATALEE trial that was recently published. This recommendation is that ribociclib for three years plus endocrine therapy, may be offered to patients with stage two or three breast cancer who would have met criteria for study entry and have a high risk of recurrence. I would note with this one, I think it's important to remember that the ribociclib that's used in the adjuvant setting is a different dosing. So it's 400 milligrams daily, three weeks on, one week off, as compared to the 600 milligrams we're using in the metastatic setting. That was the second new recommendation. As I previously mentioned, however, there were two qualifying statements. The first qualifying statement was really the panel wanted to make, because they felt that CDK4/6 therapy in the adjuvant setting may not provide meaningful clinical benefit to every single patient who would have been eligible for these two trials. The concern was especially around lower risk patients. So the early stage two breast cancer patients who were included in the NATALEE trial, and in that situation, the panel felt for some patients, the risks may outweigh the benefits. The challenge here really was that there was not a great way to pick a very specific subgroup of patient that would benefit or wouldn't benefit. So based on that, the panel really recommended taking a broad approach and considering the benefits of therapy, the risks, the costs, and of course, patient preference when making the decision about whether or not to offer these drugs in the adjuvant setting. Then the second qualifying statement was really around how to pick between the two drugs. What the panel stated was that for patients that met the criteria for both studies, they could have been in either monarchE or NATALEE, for those patients, that abemaciclib has longer follow up, has a deepening benefit over time, it's more convenient because it's two years versus three years, and it has FDA approval. So for patients, again, that would have met criteria for either study, the panel favored using abemaciclib, except if patients had some contraindication or intolerance. That is the update, both the recommendations and the qualifying statements in this updated guideline. Brittany Harvey: Understood. Thank you for reviewing both of those recommendations and the nuances between choosing between some of those options as detailed in the qualifying statements. So then, Dr. Freedman, I think Dr. Giordano has talked about this already a little bit, but what should clinicians know as they implement these new recommendations into practice? Dr. Rachel Freedman: Yeah, in the guidelines, as Sharon said, we've really tried to offer recommendations that balance the available efficacy data along with the toxicity data and even some mention of cost consideration, although we purposely can't address that in the guideline. And we just feel that all of these need to be considered in combination for the individual patient. And just like you heard, our panel felt that for those meeting criteria for both the monarchE and NATALEE trials, given all the reasons that Sharon explained, that abemaciclib may be the preferred agent for now, but we all look forward to the evolving data in this space. It's great to have another evidence-based option with ribociclib at this time, but we really acknowledge that longer term follow up will evolve these recommendations further. Brittany Harvey: Absolutely. As you mentioned, it's great to have another option in this space. So then, in your view, Dr. Giordano, how will these recommendations impact patients with early breast cancer? Dr. Sharon Giordano: I think that, overall, this is really good news for patients who are at high risk because there's now two new available therapies that they can use to help prevent recurrence. I will note, as we mentioned before, though, they do come with a price, both the cost of the drug and the additional side effects of having two or three years of an additional drug that they're taking. But having said that, I think it's always good to have new options for therapy, and we can discuss these options with the individual patients, weigh the risks and the benefits, and ultimately, we hope with longer follow up, it would be great to see if these drugs would actually improve overall survival, which is ultimately our biggest goal. Brittany Harvey: Definitely, those are key for shared decision making between patients and their clinicians. Then finally, looking forward, Dr. Freedman, what are the outstanding questions regarding the optimal adjuvant chemotherapy and targeted therapy for early breast cancer? Dr. Rachel Freedman: Well, there are a lot of outstanding questions with regard to chemotherapy. We have a lot of questions. We still have insufficient data to specify which subgroups, who may have a higher degree of nodal involvement, or what we call anatomical risk, but perhaps a favorable biology or genomics. And we don't know which subgroups still need chemotherapy. And I think this is a group many of us are struggling with in the clinic, is what to do when you have high anatomical risk, but a well behaving cancer, so to speak. And I think that's a burning question for many of us. I still think we have room to improve our adjuvant regimens and figuring out who needs more and who needs less therapy when we are going to move forward with chemotherapy. And we also, with regard to CDK4/6 inhibition, have a lot of ongoing questions. There are a lot of patients who may not benefit from CDK4/6 inhibition as much as others, and the broader population on the NATALEE trial allows us to explore this a little bit, but we're cautious about interpretation of subgroups. But the lowest risk patients on the NATALEE trial may be a group of patients that it's really important to think about when it comes to balancing that toxicity and efficacy risk, as opposed to that higher risk patient where you're sure you want to move ahead. And I think we really await the survival data from both NATALEE and monarchE, neither of which have shown a statistically significant survival advantage to date. We really need ongoing follow up of these studies, and we look forward to learning more in the years to come. Dr. Sharon Giordano: Yeah, I completely agree. It's very well said. I mean, I think one of the biggest challenges, as Rachel said, it's really hard to figure out which subset of patients are truly going to benefit and have the benefit of the drug outweigh the side effects. I hope as we get longer follow up on the studies and additional data come out, we're able to get more information so that we can really give the best therapies to the patients that need it, but also spare patients who don't need it from the additional side effects. Brittany Harvey: Absolutely. We'll await the longer term follow up of these trials and then future updates to these guidelines. So I want to thank you so much for your work to rapidly update this breast cancer guideline. And thank you so much for your time today, Dr. Giordano and Dr. Freedman. Dr. Rachel Freedman: Thanks so much. Dr. Sharon Giordano: Yeah, thank you very much, our pleasure. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full rapid recommendation update, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Karen Mustian joins us to share the latest update to the management of fatigue in adult survivors of cancer guideline from the American Society of Clinical Oncology and the Society for Integrative Oncology. Dr. Mustian highlights the recommendations across the continuum of care, including recommendations for patients with cancer-related fatigue during active treatment, after treatment, and for patients with advanced cancer or at the end of life. She also discusses interventions that are not recommended for treating cancer-related fatigue. The episode wraps up discussing the importance of this guideline for clinicians and patients, and a call for more research both on interventions and on dissemination and implementation to improve symptom management for cancer-related fatigue. Read the full guideline update, “Management of Fatigue in Adult Survivors of Cancer: ASCO-SIO Guideline Update” at www.asco.org/survivorship-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/survivorship-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00541   Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I'm interviewing Dr. Karen Mustian from the University of Rochester School of Medicine and Wilmot Cancer Institute in New York, co-chair on “Management of Fatigue in Adult Survivors of Cancer: American Society of Clinical Oncology –Society for Integrative Oncology Guideline.” Thank you for being here, Dr. Mustian. Dr. Karen Mustian: Thank you for having me, Brittany. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Mustian, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to dive into the content of this episode, Dr. Mustian, what is the purpose and scope of this updated guideline on fatigue in adult survivors of cancer? Dr. Karen Mustian: Cancer-related fatigue is one of the most common and debilitating consequences that patients experience when they go through treatment, and it can actually interfere with their ability to complete treatment and their recovery along the way. And it's not the same as a typical fatigue that you might experience from physical activity, let's say, where you can come back in and rest for a little while or take a nap or sleep, and you wake up refreshed and not feeling fatigued anymore. This type of fatigue actually needs special attention and needs to be treated with therapies.   So, this particular guideline is developed in a manner to help clinicians when patients present with fatigue, especially moderate to severe fatigue, that can be very debilitating, help patients decide what kinds of treatments they can use to reduce this fatigue. It's really important that this fatigue be reduced for a number of reasons. But some of the reasons we think of as being really critical are so that they can actually get their full treatment as prescribed, and then when finished with treatment, so they can actually resume their normal daily activities. They can keep working, they can keep engaging with their families, they can resume all those wonderful normal life activities that we hope for and that their prognosis will be a good one. Brittany Harvey: Absolutely. It's critical to address cancer-related fatigue for all adults with cancer.  Then, this guideline covers three distinct patient populations and provides recommendations for each. Starting with the first section, what are the key recommendations for patients with cancer-related fatigue during active treatment? Dr. Karen Mustian: Well, one of the things I want to mention about this guideline before I answer that question is this guideline encompasses the entire cancer trajectory. In previous guidelines for treating fatigue, we really focused on how to work with patients once they had completed their primary treatments for their cancer. This time, we're able, because the research and the literature have advanced more, to really now address what we should be doing to help patients with their fatigue while they're receiving active treatment. This can be primary treatment and/or maintenance therapies, but then also once they're done with treatment and they are in the recovery stage. And then also the third area is how should we help patients with advanced cancers with their fatigue that they are experiencing?  And I believe that you just asked me how we should be working with patients really during active treatment. This guideline, when we reviewed the literature, there's really good evidence to suggest that for people undergoing cancer treatment, clinicians should recommend exercise, cognitive-behavioral therapy, mindfulness-based programs, and Tai Chi or Qigong as first-line therapy to reduce the severity of fatigue that patients can experience during treatment. We also found that the literature suggests that psychoeducation and American ginseng may also be recommended in adults undergoing cancer treatment. Brittany Harvey: Understood. Thank you for providing those key recommendations for patients with cancer-related fatigue during active treatment.  Then, following those recommendations, at the next point in the cancer trajectory, what does the expert panel recommend for patients with cancer-related fatigue after treatment? Dr. Karen Mustian: Well, for survivors after treatment, the literature is also strong in that clinicians should be recommending also exercise, again, cognitive-behavioral therapy, and mindfulness-based interventions and programs. There's also a good amount of data to suggest that we should be recommending yoga, acupressure, and moxibustion for cancer-related fatigue after completion of treatment. Brittany Harvey: I appreciate you reviewing those recommendations as well.  Then that final third population that you previously mentioned, what are the key points for the management of cancer-related fatigue for patients with advanced cancer or at the end of life? Dr. Karen Mustian: For patients at the end of life, we should be offering those individuals cognitive-behavioral therapy and corticosteroids. Brittany Harvey: Thank you for reviewing all of those recommendations for patients with cancer-related fatigue during active treatment, after their treatment, and for patients with advanced cancer.  Are there additional recommendations that were made by the expert panel that we should know about treating cancer-related fatigue? Recommendations for things that we should not be doing to treat cancer-related fatigue? Dr. Karen Mustian: One of the things that's also characteristically different about this particular guideline update for ASCO is that this time we actually have research to suggest that there are some interventions that historically may have been used, but the research is actually suggesting that they should not be recommended at this time. The guidelines now state that clinicians should not recommend L-carnitine or antidepressants, wakefulness agents, or routinely recommend psychostimulants to manage symptoms of cancer-related fatigue. One of the things that this really highlights is the recommendation to pull back on the use of pharmaceutical products as a first-line therapy for treating fatigue and to really look at behavioral interventions which are showing the strongest evidence in the research in terms of effectiveness, both during treatment, after treatment, and for our patients with advanced cancer, and to really promote these behavioral interventions for patients rather than just reaching right for that pharmaceutical product.  There are still instances where pharmaceuticals may be really important for patients, such as if someone tries behavioral therapies and they fail, for example, or if someone has fatigue that is just absolutely so severe that they cannot even give a good effort or attempt to trying something like exercise or cognitive-behavioral therapy or mindfulness-based programs. You know, even considering that most of the cognitive-behavioral therapy and mindfulness-based programs don't require physical activity, they're very low intensity types of behavior change. And that's really a big area where these guidelines also differ in the update from previous guidelines.  Brittany Harvey: Absolutely. I appreciate you reviewing those so that we know what strategies and treatments also should not be used and how we need to tailor our interventions to specific patients and their needs.  So then, in your view, Dr. Mustian, what is the importance of this guideline and how will it impact both clinicians and patients with cancer-related fatigue? Dr. Karen Mustian: I've seen a lot of ASCO guidelines and helped with a lot of ASCO guidelines, and one of the things that I think is really great about this particular guideline for cancer-related fatigue is, I'll reiterate, this is one of the most prevalent, debilitating toxicities experienced by virtually all cancer patients at some point during their time being treated or in recovery. And I'm really pleased to see that the research has come far enough that we now actually have interventions that we can recommend strongly, and then we also have other interventions that we recommend that the evidence is still growing for.  What's also nice about this, and what's really going to be impactful for patients, as I just said, is that the recommendations are not focused on pharmaceuticals. Patients already take a lot of pharmaceutical products, we have to worry about polypharmacy and all the side effects associated with that, especially in our elderly populations. This guideline gives clinicians and patients not just one or two, but several behavioral interventions that they can use that, if used in the correct way, as stated in the guidelines, stand an excellent chance of reducing the amount of fatigue that they experience. So, it really is going to change the landscape of care for patients. It's also going to change the landscape of what clinicians have to offer in their toolkit for treating patients. And I know that oftentimes we think it's easy for a physician to recommend a pharmaceutical product. But I also know that a lot of oncologists love being able to recommend lifestyle interventions to really help their patients with side effects and toxicities. And that's exactly what this guideline is offering. And I think it's just going to provide a wonderful place for a clinician and patients to come together to have conversations about what the guidelines say is effective, and to allow them to have a conversation surrounding choice. Which one seems to be the best fit? Which one would a patient actually like to try? Which of these lifestyle interventions does the patient think they have the best chance of succeeding with both in terms of accessing it in their community, adhering to it, being able to do it so that they can actually derive the benefits that we expect to see. That's really one of the key components of the efficacy of these interventions as well, is what really is going to determine, ultimately, how well these interventions work is working together to pick the one that the patient feels that they can actually do and accomplish in order to receive the benefits. It really is going to change the landscape of how we work with symptom management surrounding fatigue. Brittany Harvey: Yes. As you mentioned, it's great to have these multiple evidence-based recommendations to have a real impact for patients. You also just noted that evidence is still growing in some areas. So what future research is needed regarding the management of cancer-related fatigue in adult survivors of cancer?  Dr. Karen Mustian: I think oftentimes when we see a guideline come out, many times people say, “Well, we have the answers now, so we don't need to fund any more research in that area.” Or maybe it becomes less of a priority. For all that we do have these treatments to recommend now, we're still really very in the early stages of being able to identify, characterize and accurately provide therapies and treatments for cancer-related fatigue. When I look back at the history of nausea and vomiting and where we've come in the decades of research that has ensued since the first initial findings on that. I think fatigue is still very much in its early years.   Some of the things that we still don't necessarily know when it comes to these kinds of interventions, and I can tell you we struggled with in the guideline committee, is what is the actual dose of some of these behavioral interventions? I think when we prescribe a medicine, we think, “Oh, you need this particular dosage of this particular agent. You take it this many times a day, this many times a week for x number of weeks, and there you go.” With behavioral interventions, it's a little more complex. And so really getting down to the nitty-gritty of defining exactly what type of exercise, the intensity of that exercise, exactly how many minutes a day, exactly how many minutes a week do you have to do? We weren't really able to get our recommendations refined to that degree, and I think future research that really wants to be in service of clinicians and patients should work towards defining specific prescriptions of these interventions.   Exercise, I just gave that example, but it's the similar kind of approach for cognitive-behavioral therapy. What are the specific components that need to be included? What does the ratio of focus on those different components need to look like? Also, the same with Tai Chi, Qigong moxibustion, acupressure that we mentioned - really refining those specific prescriptions, I think, is something that we need research on, and that will take us to the next step, where we have patients doing enough that they get the effect that they want, but not wasting their time, effort, energy, and finances doing too much that they don't need to do in order to achieve the benefit that we hope for.   For some of the recommendations that are not strong, we still need large, definitive, randomized clinical trials on those interventions. So, for example, we talk about that we may recommend psychoeducation and American Ginseng for patients undergoing cancer treatment. We need more research in that area in order to be able to really say whether or not we should be offering that for patients undergoing treatment. And specifically, those large, definitive, phase III randomized clinical trials, talking about trials that also could be done across multiple centers where we can have more generalizable populations, different kinds of communities where those interventions are being delivered, rural dwelling communities, for example. And then, of course, there's always the need for newer and better interventions. Some of these interventions have very decent effect sizes in terms of their outcome, but it would be wonderful to actually find an intervention that completely mitigated cancer-related fatigue, and it was completely gone, never to return. I think we're still in some ways waiting for that intervention to be developed. And I also would say, even though we're not recommending pharmaceuticals quite a lot in this guideline, they're not our first-line therapy, there's still always the opportunity to identify molecular targets that really could help with remediating cancer-related fatigue. So there's still a plethora of research to be done out there and things that we don't know.   And then lastly, and very much importantly, we need to do research and dissemination and implementation. Behavioral interventions are really challenging to deliver. So unlike a doctor recommending a pharmaceutical product where they can write a prescription, and then the patient gets the prescription from the pharmacy and they have what they need, supposedly understanding how to prescribe these interventions for patients, or even understanding how to refer them to places in communities where they can actually get a credible practitioner that is using an evidence-based approach that is known for being one of the types of yoga or exercise, or mindfulness-based stress reduction or CBT, that will actually have a positive influence on fatigue is also challenging. And so we need that dissemination and implementation research  - that I do believe is going to be also really key in the next decade at changing the landscape of what this toxicity looks like in the patient experience of cancer. Brittany Harvey: Definitely, these all will be key to understanding the best options for all patients, and we'll look forward to continued research in these areas to fuel future guideline updates and improve management of cancer-related fatigue in all adults with cancer.  So, I want to thank you so much for your work developing this guideline, and thank you for your time today, Dr. Mustian. Dr. Karen Mustian: Oh, it's such a pleasure. I did not develop this guideline alone. I definitely want to say thank you to all my colleagues who worked very diligently and very hard on digesting the research and making these recommendations. They are representative from institutions all across the United States. A very wonderful expert panel. Thank all of them very much and give them the credit that they are due for all their hard work. And thank ASCO for supporting these efforts for clinicians and patients. And Brittany, thank you very much for having me. Brittany Harvey: Absolutely. A big thank you to the whole panel.   And thank you also to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/survivorship-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Dr. Debra Lundquist, PhD, RN and Dr. Arun Ghoshal, MD, MBBS discuss the new update to the palliative care for patients with cancer guideline developed by an interdisciplinary Expert Panel. They share the key updated recommendations on the most effective palliative care interventions, how these recommendations relate to other supportive care services, interventions for family caregivers, care partners, and communities, referrals to specialist palliative care services, and specific strategies for the integration of palliative care for patients with hematologic malignancies and those on early phase clinical trials. Dr. Lunquist and Dr. Ghoshal also discuss the contextual factors that affect equity at the intersection of palliative and oncology care, the impact of this guideline refresh for clinicians and patients, and future innovations in the field of palliative care. Read the full guideline update, “Palliative Care for Patients with Cancer: ASCO Guideline Update” at www.asco.org/supportive-care-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/supportive-care-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00542 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO’s podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.    My name is Brittany Harvey, and today I'm interviewing Dr. Arun Ghoshal from Princess Margaret Cancer Center and Dr. Debra Lundquist from Massachusetts General Hospital, authors on, “Palliative Care for Patients with Cancer: ASCO Guideline Update.” Thank you for being here, Dr. Ghoshal and Dr. Lundquist. Dr. Ghoshal: Thanks, Brittany. Thank you for having us here. Dr. Lundquist: Yes, it's a pleasure. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Lundquist and Dr. Ghoshal, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to start us off, Dr. Lundquist, what prompted this guideline update, and what is the scope of the current update for palliative care for patients with cancer? Dr. Lundquist: Sure. So the goal of this refresh is really to provide oncology professionals with current recommendations regarding palliative care and assess which of the 2016 recommendations remain valid. The scope did increase to also include hematologic malignancies and participants of early phase clinical trials. In addition, this was an opportunity to reflect more recent evidence around the understanding of linguistic, geographic, ethical, and contextual factors that affect equity at the intersection of palliative and oncology care. This update also increased discussion about the inclusion of palliative care, as I mentioned earlier, for the enrollment of patients in clinical trials. And also, in terms of the equity piece, there is also a companion manuscript with the guidelines that focused on the health equity in the oncology palliative care setting. Brittany Harvey: Excellent. Thank you for setting the stage for this update, Dr. Lundquist.   So then next, I'd like to review the key updated recommendations for our listeners. So starting with clinical question one, Dr. Ghoshal, what are the key recommendations regarding the most effective interventions to provide palliative care to patients with cancer? Dr. Ghoshal: As we know, healthcare providers should proactively engage in the early integration of specialized, interdisciplinary palliative care teams for patients diagnosed with advanced solid tumors, and as mentioned, not only solid but also hematological malignancies. The most important thing is that palliative care should be offered not only for inpatients but also for outpatients, and oftentimes, when we talk about early palliative care, it is in concurrence with active cancer treatment. So if you want to talk about the core components of such an effective palliative care practice that would encompass establishing a nurturing rapport and relationships with patients and their family caregivers to foster trust and open communication. And obviously, it will encompass symptoms, distress, and functional limitations comprehensively, including but not only limited to pain, dyspnea, fatigue, sleep disturbances, mood disorders, nausea, and constipation.   Another important part is providing education and facilitating discussions to enhance patients' understanding of their illness and prognosis. That means we need to play an active part in clarifying the treatment goals through a shared decision-making process that aligns the patient's values and preferences with their physicians. And apart from that, in this revised guideline, the key evidence about question number one, which is from 2016, and updated to the present is mainly based on three trials with a low risk of bias. These three studies actually demonstrated that early referral to specialized palliative care of patients with advanced cancer led to improvement in the quality of life and also mood, which was a secondary outcome in that study and the higher likelihood of discussing or documenting end-of-life care preferences. I know that the link to the full documents are in the show notes, and I would encourage the listeners to refer to the supplement to the paper that is coming out in the Journal of Clinical Oncology for understanding and getting a detailed insight into the studies which are included in these recommendations. Brittany Harvey: Absolutely. Early integration of all those aspects of palliative care that you just detailed are imperative. And as you just mentioned, the listeners can find a link to the full guideline in the show notes of this episode to refer back to the more detailed aspects of the guideline.  So following those recommendations, Dr. Lundquist, what does the expert panel recommend regarding how palliative care services should relate in practice to other supportive care services? Dr. Lundquist: The panel examined the role of the use of additional supportive care services that focus on services including nurse navigation, lay navigation, community and home health care, as well as geriatric oncology, psycho-oncology, pain services, and telehealth services. And findings supported that models of delivering palliative care with the use of other services as well can really improve the patient experience. And one of the ways of doing that, more utilization of standardized assessments of symptoms, certainly, but also encompassing the multidimensions of distress, spirituality, and psychosocial factors. And then emphasizing discussions around prognostic and treatment options to really get a better sense about the patients' understanding of their prognostic awareness, which may also lead to more improved communications around advanced care planning.  And the studies around this guideline supported that most pragmatic approaches to ensuring that patients benefit from palliative care is really through the involvement of this interdisciplinary team and looking from a broad lens, looking at all their potential palliative care needs that may need to be met. But certainly, referral to a specialized interdisciplinary palliative care team is also very important. But it really is where that step before is really looking at the whole experience of the patient and where they are in their cancer trajectory.   Brittany Harvey: Excellent. Yes, incorporating all of those additional supportive care services really benefit patients.   So then beyond these recommendations for patients with cancer, Dr. Ghoshal, what are the recommendations for interventions that are helpful for family caregivers, care partners, and communities? Dr. Ghoshal: This is a very pertinent question for palliative care practitioners. So, interesting to note that the panel found that there is limited data that exist on how best to support the caregivers of patients with advanced cancer, and especially so in under-resourced settings. And also, most of the evidence that came from the literature is from data which was collected in studies before the COVID-19 pandemic. So the previous guideline stressed the option of phone interventions for those in rural or under-resourced areas. But as we know, with the growth of telehealth and telemedicine related to the pandemic, especially after the pandemic, more people are used to such interventions, more people probably could access and feel comfortable with virtual care. So telehealth, app-based support, and virtual care options, which are probably available and largely familiar to many people, could potentially allow increased access to support services. Talking about these support services, the focus that has been mostly seen in literature are about education and training programs to empower the caregivers of these patients with advanced cancer, psychosocial support services for emotional well-being of the carer as we know that it can be pretty tough for someone to deal with cancer and also for their caregivers. Also sometimes practical assistance with daily tasks, if possible, to ease the burden of caregiving. Sometimes importance is there on respite care to provide temporary relief for these caregivers. Community supports can play a big role for sharing the resources. Social connections can also play an important part when it’s available. And also very important and we all know that advance care planning discussions to ensure patients' wishes are known to their caregivers. And of course, we must keep this in our mind that cultural sensitivity in caregiving practices is very important to accommodate people from diverse backgrounds. So mostly these are interventions, as mentioned in the guideline, which are aimed at supporting caregivers in their role to alleviate their stress, and to improve the overall caregiving experience for both caregivers and patients with cancer. Brittany Harvey: Thank you for reviewing the recommendations for support services for both caregivers and care partners in addition to patients with cancer.  So then Dr. Lundquist, you previously mentioned referral to specialist palliative care services. Who does the expert panel recommend should be offered or referred to palliative care services, and when should those referrals occur?  Dr. Debra Lundquist: And as the panel looked at referral to palliative care services, we looked at essentially patients with advanced solid tumors or hematologic malignancies, particularly, those patients with cancer who have unaddressed physical needs, psychosocial needs, and spiritual distress, and as we just heard, the importance of including the caregivers in care and offering palliative care. And the caregivers may include family members, chosen family, friends of individuals who have advanced cancer. And then also looking at including patients that we’ll talk a little bit later about the patients that are on phase one clinical trials as well and why they might be another population to be considering.  But certainly, as we’ve mentioned a little bit already, early in the course of the advanced cancer diagnosis is a very important time to initiate the palliative care. The panel recommends not waiting for the discontinuation of antineoplastic therapy or treatments around the cancer diagnosis, but rather focusing on the specific palliative needs of the individual and really thinking more about it occurring when the patient is getting their active treatment as well in a way to better support them while they potentially may be experiencing side effects from their treatments, from their disease, and thinking about this earlier in the disease continuum.  Ideally, clinicians and organizations really need to prioritize the assessment of these dimensions of the patient experience for earlier recognition of their needs at the time of diagnosis of their advanced cancer, but to also really be thinking about while the patients are still receiving active treatment, to really be identifying and determining what other palliative care needs may need to be addressed.  Brittany Harvey: Definitely, those are key considerations for clinicians, and I thank you for defining what early referral means in these circumstances.  So, you both mentioned that this guideline expanded to patients with hematologic malignancies. Dr. Ghoshal, what strategies are recommended for the integration of palliative care into the care of patients with hematologic malignancies?  Dr. Arun Ghoshal: The updated review this time identified three publications. Actually, two of those publications are randomized controlled trials including patients with hematologic malignancies, especially those with acute myelogenous leukemia and those receiving hematopoietic stem cell transplantation. It is important because the trajectory of illness for hematologic cancers and solid tumors can be a bit different. Patients with hematologic malignancies, despite newer therapies offering long-term survival, often face significant side effects. Compared to the solid tumor patients, those with hematologic cancers experience higher hospitalization rates, frequent intensive care unit admissions, and unfortunately, the rates of in-hospital deaths are also more in these patients. And as a result of that, the typical length of stay in hospice is shorter for these patients. Regardless of prognosis, the recommendations state that proactive palliative care should begin at diagnosis and continue throughout the illness trajectory and survivorship of these patients with hematologic cancers.   Historically, integrating specialist palliative care has been infrequent in this group of patients due to misconceptions, and obviously, limitations. However, the latest evidence that we’re talking about supports the benefits of palliative care for patients with hematological cancers, especially, improving their quality of life and psychological outcomes. However, given the paucity of studies in this domain, further research is needed to expand the recommendations beyond the studied population. Brittany Harvey: Thank you for highlighting the specific needs and recommendations for this patient population.   So then, Dr. Lundquist, for the final clinical question, you’ve already touched on this a little bit. But what is the role of palliative care for patients with cancer participating in early phase cancer clinical trials?  Dr. Debra Lundquist: As I mentioned earlier, the panel this year included this patient population in the refresh of the guidelines. And the early phase clinical trial population is a population of patients who present functionally well, however, most present with advanced disease and have frequently received multiple lines of therapy prior to coming to the clinical trial. They may experience a distinct set of symptoms and concerns with unique supportive and palliative care needs. When we looked at the literature, there is a growing body of research around this, although it is still quite small at this time. Certainly an area for future research.   Patients who are participating on early phase clinical trials come to the trial and they may be struggling to cope with the uncertainty regarding their future, as well as symptoms they may be experiencing and really not knowing what that clinical trial experience is going to look like. So the panel, as we were looking through the literature, it’s becoming more clear that this is a patient population who may have existing physical and psychosocial concerns who would possibly benefit from earlier identification of their palliative care needs as well as intervention with palliative care support coming on to the clinical trial. With the research being limited, the focus on better understanding their palliative care needs is an area for the future that we really may want to be considering more in terms of improving the patient experience. This is a patient population who, I think, in terms of ongoing research, we’re starting to see the benefits and looking at their unique dimensions of their care as they come onto the trial. But then providing  the opportunity to enhance their experience and also better identify their distinct supportive care needs may, in fact, enhance their quality of life while they're on the early phase clinical trial. Brittany Harvey: I appreciate you both reviewing all of this updated and expanded recommendations from the expert panel.  In your view, Dr. Ghoshal, what is the importance of this update and how will it impact both clinicians and patients?  Dr. Arun Ghoshal:  So 2015 to 2023, the time and the duration that the update took into consideration, you won’t believe, we got 52 randomized control trials on the subject, and one systematic review, which is the evidentiary basis for the guideline recommendations. So the ASCO guideline update on palliative care for patients with cancer underscores the importance of a comprehensive, patient-centered approach to care that prioritizes symptom management, communication, and support for not only patients but also their families. It distinguishes itself through its rigorous methodology, the expert consensus from a wide array of people who take part in these updates, and also, there is a special section for all the recommendations as far as clinical relevance is considered. The updates are very timely and also comprehensive for sure. So all of these features make it a valuable resource for clinicians who want to seek guidance on providing optimal palliative care to patients with cancer.   I believe that the uptake, as far as possible, by institutions and physicians, factoring physicians all around the world, these guidelines would benefit the patients by providing evidence-based recommendations that improve symptom management, enhance care communication, and shared decision making, ultimately ensuring timely access to palliative and supportive care services. The uptake will support the caregivers and hopefully will help a long way in optimizing the end-of-life care for these patients suffering from cancer.  Brittany Harvey: Definitely, we hope that these updated guidelines are a useful resource for clinicians, as you pointed out, to provide better end-of-life care for all patients with cancer.   So, you both touched a little bit on the limited evidence and some future research opportunities. So finally, to wrap us up, Dr. Lundquist, what are the outstanding questions and future research needed on palliative care in patients with cancer? Dr. Debra Lundquist: As we’ve been hearing about in our conversation today, the findings and the benefits of palliative care, they’re well known. We know the difference palliative care makes in the life of patients that are experiencing or living with advanced cancer as well as their caregivers and their families. But certainly, more studies are needed to explore more innovative and other models of care. Because we also need to acknowledge that as much as we want every single person to have the opportunity to get palliative care, the workforce is not going to support that. So this is an important time to think about innovative, potentially scalable, and compelling strategies to address the unmet needs of patients in order to deliver palliative care. Innovative approaches are needed, particularly, to overcome the shortage of the workforce in order to better support the unique needs of our patient population. So as we’re thinking forward, novel application of interventions to address unmet needs tailored to the unique needs of patients across the disease trajectory, and that may include collaborative care models, telehealth, additional training and resources, for example, nurses; advanced practice providers. But as we’re doing that, we really need to be thinking about how we’re going to design, develop, and test these interventions in order for them to be scaled appropriately. And then how do we implement and disseminate across different settings, rural, urban, different locations, in order to best meet the needs of this patient population.       Brittany Harvey: Absolutely. Those are important questions for us all to consider moving forward, and we'll look forward to future research in these areas to continue to provide optimal palliative care to all patients.  So I want to thank you both so much for all of your work on this guideline update, and thank you for taking the time to share the important nuances of this guideline with our listeners today, Dr. Lundquist and Dr. Ghoshal.  Dr. Arun Ghoshal: It's been a pleasure being here.  Dr. Debra Lundquist: Thank you very much, Brittany. It was a wonderful opportunity. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.  The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

Dr. Douglas Peterson presents the latest evidence-based guideline from ISOO, MASCC, and ASCO on the prevention and management of osteoradionecrosis (ORN) in patients with head and neck cancer treated with radiation therapy. He covers topics such as recommended initial workup, best practices for prevention of ORN of the head and neck before and after radiation therapy, nonsurgical and surgical management of ORN, and management of adverse events associated with ORN. Dr. Peterson also comments on the importance of this guideline and what researchers should address moving forward. Read the full guideline, “Prevention and Management of Osteoradionecrosis in Patients with Head and Neck Cancer Treated with Radiation Therapy: ISOO-MASCC-ASCO Guideline” at www.asco.org/head-neck-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/head-neck-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.02750.   Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts, bringing you timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all our shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey and today, I'm interviewing Dr. Douglas Peterson from UConn Health, lead author on “Prevention and Management of Osteoradionecrosis in Patients with Head and Neck Cancer Treated with Radiation Therapy: International Society of Oral Oncology, Multinational Association for Supportive Care in Cancer, American Society of Clinical Oncology Guideline.” Thank you for being here, Dr. Peterson. Dr. Douglas Peterson: Thank you, Brittany. My pleasure to be here. Brittany Harvey: Before we discuss the guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensures that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Peterson, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to dive into the topic we're here to discuss, Dr. Peterson, could you first provide an overview of the scope and purpose of this joint ISOO-MASCC-ASCO guideline? Dr. Douglas Peterson: I'll be pleased to do so, Brittany. Again, thank you for the opportunity to represent the panel in this guideline. The panel has strived to present a guideline that brings consistency in clinical practice regarding prevention and management of osteoradionecrosis of the jaw (ORN) based on the highest quality contemporary science. Given the mechanistic and clinical complexity of ORN, we also stress the importance of interprofessional oncology care of these patients. The team includes, but is not limited to, clinicians representing radiation oncology, head and neck surgery, medical oncology, otolaryngology, dental medicine, oral medicine, oral oncology, oral and maxillofacial surgery, and patient advocacy organizations. So it really is a collective enterprise that we bring to bear in the guideline.  In some cases, the panel has been fortunate to be able to utilize a high quality evidence base in the literature upon which we could build strong recommendations. In selected other cases, however, we utilized informal consensus given the low evidence quality in the field. The recommendations presented have been carefully framed in this context, with the goal of providing state-of-the-science guidelines in clinical decision making and management of ORN. I'd also like to point out that the guideline brings linkage to other guidelines published by ASCO and other major oncology organizations, regarding management of symptoms and other supportive care needs associated with ORN. These companion guidelines include addressing pain, dysphagia, oral care, trismus, and psychosocial impact and survivorship, to name a few. I'd also like to say that combining the expertise of ISOO, MASCC, and ASCO has provided an important opportunity to produce this guideline. This has been a comprehensive effort by many experts. In addition to the outstanding input from the panel, I am also personally so very grateful for the expert input from ASCO's Evidence-Based Medicine Committee, as well as endorsements from other key organizations, including the American Head and Neck Society, the American Society for Radiation Oncology, and the American Academy of Oral Medicine as endorsees of the guideline. Finally in addition, Dr. Nofisat Ismaila’s leadership as ASCO staff has been absolutely invaluable as well.  Brittany Harvey: Excellent. I appreciate you providing that background on the development of this evidence-based guideline, which was developed by a multi-organizational and multidisciplinary panel.   So to dive into the key recommendations of this guideline, this guideline addresses six clinical questions. So, starting with question one, what key points would you like to highlight regarding how ORN is characterized, graded, and reported, and what is the recommended initial workup for patients?  Dr. Douglas Peterson: Osteoradionecrosis of the jaw of the mandible and maxilla should be characterized in the view of the panel as a radiographic, lytic, or mixed sclerotic lesion of bone, and/or visibly exposed bone, and/or, importantly, bone probed through a periodontal pocket or fistula. In the latter case, the clinical appearance of exposed bone may be extremely subtle. ORN is occurring within an anatomical site previously exposed to a therapeutic dose of head and neck radiation therapy. So we have a combined radiographic/clinical approach characterizing the lesion in the context of the patient having received previously a therapeutic dose of head/neck radiation therapy. We do recommend that clinicians evaluate ORN based on the most contemporary staging system, the ClinRad system, which is cited in the publication itself. We also advocate for the use of the ClinRad staging system not only in clinical assessment of patients, but also in clinical trials moving forward. We’ll touch a little bit later on future research opportunities as well.  Finally, the initial evaluation of ORN should include a clinical intraoral examination, and again, the appearance of exposed bone may be extremely subtle, and/or a formal radiographic examination. The guideline delineates the various types of radiographic examinations that we recommend.  Brittany Harvey: Understood. Thank you for reviewing those recommendations regarding reporting and characterization of ORN, as well as the workup.   The next section of the guideline, it focuses on best practices to prevent ORN of the head and neck prior to radiation therapy. What are the key recommendations of that section?  Dr. Douglas Peterson: As with other adverse events in oncology patients, prevention is key. Prevention of ORN does require interprofessional management. The guideline lists several key recommendations along these lines. Now, an important caveat in what the guideline presents is that the target coverage of the tumor should not be compromised in order to avoid radiation dose to bone. So that’s a very important caveat. Now having said that, focused effort should be made to reduce the mean dose to the jaw and the volume of bone receiving above 50 Gy whenever possible. So it’s really a balance between maximizing target coverage of the tumor while limiting exposure to normal bone. In addition, a dental assessment by a dentist and dental specialist, if possible, is strongly advised prior to therapeutic-intent radiation therapy. The purpose of this assessment by the dental team is to identify and remove teeth which will place the patient at risk of developing ORN during the patient’s lifetime, and to comprehensively educate the patient about the lifelong risk of ORN. Dental extraction in advance of radiation is often a consideration to these patients, and if clinically indicated, should occur at least two weeks prior to the commencement of radiation therapy. Now having said that, in the setting of a rapidly progressive tumor, extraction should be deferred and not cause delay in the initiation of radiation therapy. Brittany Harvey: So you just touched on key points of prevention prior to radiation therapy. Following those recommendations, what does the expert panel recommend regarding best practices to prevent ORN after radiation therapy? Dr. Douglas Peterson: This can be a challenging clinical issue. So the panel recommends that before finalizing dental treatment plans that may include extractions in patients with a history of head and neck radiation therapy, a review of the radiation therapy plan should be performed with particular attention focused on dose to the mandible and maxilla. For teeth in areas of high-risk for ORN, alternatives to dental extraction may be possible, for example, root canal or endodontic procedures, crowns, or dental restorations, or dental filling should be offered unless the patient has recurrent infections, intractable pain, or other symptoms that cannot be alleviated without extraction. So it really becomes a combined clinical decision making effort between the dental team and oncology team.  One controversial area has been hyperbaric oxygen being administered prior to dental extractions in patients who have received head and neck radiation therapy previously. The panel does not recommend routine use of prophylactic HBO prior to dental extractions in these patients who have received prior head and neck radiation therapy. However, the evidence base here is limited with low quality and we offer a weak strength of recommendation. It is a controversial area, so we did also include a qualifying statement that prophylactic HBO may be offered to patients undergoing invasive dental procedures at oral sites where a substantial volume of the mandible and/or maxilla receive at least 50 Gy. This is an area of controversy. We can talk about this in the future research directions, but clearly, new high quality research related to the role of HBO in the management of these patients is needed.  Brittany Harvey: Definitely. Thank you for touching on those points and that area of controversy. We can definitely touch on that a bit later as we talk about future research in this field.  As you mentioned, Dr. Peterson, this guideline addresses both prevention and management. So, in moving into the management of ORN, how should ORN be managed nonsurgically?  Dr. Douglas Peterson: The guideline relative to nonsurgical management of ORN is focused on the use of pentoxifylline. Now this maybe used in, and this is important, in cancer-free patients with mild, moderate, and severe cases of ORN. But pentoxifylline, the guideline also notes, is most likely to have a beneficial effect if the treatment is combined with tocopherol, antibiotics, and prednisolone as well. So there’s clinical judgment involved in the nonsurgical management of ORN, centered with pentoxifylline in combination with tocopherol, antibiotics, and prednisolone. Brittany Harvey: Understood. And then expanding on the management of ORN, what are the key points for surgical management of ORN? Dr. Douglas Peterson: The panel offered several recommendations for which the strength of the recommendations was strong. Just to cite a few, in partial thickness ORN as defined by the ClinRad stage one and two that we talked about earlier, surgical management can start with transoral minor interventions which can lead to resolution over time. It may take time. It may take weeks or even a few months. Now this minimally invasive surgery may include debridement, sequestrectomy, alveolectomy, and/or soft tissue flap closure. Furthermore, small defects, clinically, for example, less than 2.5 cm in length, may heal spontaneously with local topical measures such as we described. It is recommended that larger defects, larger than 2.5 cm, in general be covered with vascularized tissue.  Brittany Harvey: Appreciate you reviewing those recommendations regarding surgical management of ORN. So to wrap up our discussion of the recommendations with the final clinical question, what is recommended for assessment and management of adverse events associated with ORN?  Dr. Douglas Peterson: This is a really important area as well in addition to prevention and management of ORN per se. The panel recommends that patients should be assessed by their healthcare providers for the presence of adverse events at the time of ORN diagnosis and periodically thereafter until the adverse event resolves based on patient status including any interventions or the adverse events that are clinically indicated. The panel and its literature evaluation learned that there is a relative lack of data specifically directed to the management of adverse events associated with ORN. However, this is such an important area that we wanted to address it head on. And so the management we recommend should be informed by pertinent available other guidelines that had been developed for analogous symptoms and/or disease states. The guideline provides links to these companion guidelines developed by ASCO as well as by MASCC and ISOO, the European Society of Medical Oncology, and NCCN. And so in the guideline we provide links on management of adverse events as produced by these other organizations. Table 3 presents a summary of the guidelines that address symptoms and supportive care needs associated with ORN.  Brittany Harvey: Thank you for reviewing all of these recommendations. It's clear that the panel put a lot of work and thought into these recommendations and provided needed guidance in areas with limited evidence. We’ll have links available in the show notes for listeners to be able to go and read these recommendations for themselves and refer to the tables that you mentioned.  So in your view, Dr. Peterson, what is the importance of this guideline and how will it impact clinicians and patients with head and neck cancer? Dr. Douglas Peterson: As we talked about throughout this podcast, the guideline is designed to synthesize the contemporary science regarding ORN and translate that into recommendations for clinical practice in both prevention and management. As noted in the guideline, oncologists plus other interprofessional healthcare providers have been directly involved in the creation of the guideline, that interprofessional theme, which we believe is so essential given the mechanistic and clinical complexity of ORN.  Now, in addition to the expertise of the panel, the pending widespread distribution of the guideline represents an additional important opportunity for extending the impact across clinical oncology. So in addition to the publication in the Journal of Clinical Oncology, dissemination by MASCC and ISOO as well as our endorsees, the American Head and Neck Society, the American Society for Radiation Oncology, and the American Academy of Oral Medicine will also be key in broadening the impact and hopefully the utilization of the guideline. And members of these organizations may very well be involved in the management of these patients as well.  And then finally, the guideline is also designed to stimulate future research based on current gaps of the knowledge and we touched on some of those gaps, for example, with HBO for which new high quality research is needed.   Brittany Harvey: Absolutely. It’s great to have so many partners in this guideline and we hope that this guideline will have a large impact for patients with head and neck cancer to improve their quality of life.   So then your final comment leads nicely into my last question and that we’ve already talked a little bit about some of the future research opportunities that this guideline highlights. So, to wrap us up, Dr. Peterson, what are the outstanding questions regarding osteoradionecrosis of the jaw secondary to head and neck radiation therapy in patients with cancer?  Dr. Douglas Peterson: There are several key areas that the panel identified as we went through a rigorous review of the highest quality literature. Some of the key areas to address moving forward include: prospective studies are needed to evaluate the clinical presentation, trajectory, and response to treatment of ORN-related symptoms and function impairment, in other words, the adverse event side of the story. In addition, social determinants of health, quality of life, and psychosocial impact of ORN warrant further investigation in head and neck cancer survivors as well. In addition, new research including randomized controlled trials and prospective multicenter trials regarding the systemic and surgical treatment of ORN is also warranted, and we touched on, for example, hyperbaric oxygen. Hyperbaric oxygen has been a long standing management strategy of ORN. However, the trials to date are of limited quality in relation to supporting its use. So high quality new research related to the role of HBO in these patients is needed.   And the expert panel also encourages creation of predictive tools, a priori tools, directed to development, grading, and staging of ORN. These could include, for example, bone turnover markers and genetic markers to name two. And finally, the research opportunities that are presented in the guidelines such as what I briefly summarized today should ideally be addressed in large prospective multicenter observational studies of risk, outcomes, and financial cost of ORN or the various treatment strategies that are highlighted in the guideline.    Brittany Harvey: Excellent. Well, we’ll look forward to research that addresses those outstanding questions and I want to thank you so much for your all your work on this guideline and for taking the time to share the highlights of this guideline with me today, Dr. Peterson.  Dr. Douglas Peterson: Thank you. My privilege to do so, Brittany. Brittany Harvey: And thank you to all our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/head-neck-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app in the Apple App Store or the Google Play Store. If you have enjoyed what you heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Raymond Chan and Dr. Larissa Nekhlyudov share the newest standards and practice recommendations from MASCC and ASCO on survivorship care for people with advanced or metastatic cancer. They discuss highlights of the standards across seven domains: person-centered care, coordinated and integrated care, evidence-based and comprehensive care, evaluated and communicated care, accessible and equitable care, sustainable and resourced care, and research and data-driven care. Drs. Nekhlyudov and Chan also comment on the impact of these standards for clinicians and for patients with advanced and metastatic cancer and the goal of providing high-quality evidence-base survivorship care for all patients. Read the standards, “Survivorship Care for People Affected by Advanced or Metastatic Cancer: MASCC-ASCO Standards and Practice Recommendations” at www.asco.org/standards. TRANSCRIPT These standards, recommendations, and resources are available at https://asco.org/standards. Read the full text of the standards and review authors’ disclosures of potential conflicts of interest in the JCO Oncology Practice, https://ascopubs.org/doi/10.1200/OP.23.00716.  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I'm interviewing Dr. Larissa Nekhlyudov from Brigham and Women's Hospital and Harvard Medical School, and Dr. Raymond Chan from Flinders University, authors on, “Survivorship Care for People Affected by Advanced or Metastatic Cancer: Multinational Association for Supportive Care in Cancer (MASCC) and American Society of Clinical Oncology (ASCO) Standards and Practice Recommendations”. Thank you for being here, Dr. Nekhlyudov and Dr. Chan. Dr. Raymond Chan: Thank you for having us. Dr. Larissa Nekhlyudov: Great to be here. Brittany Harvey: Then, before we discuss these standards, I'd like to note that ASCO takes great care in the development of its guidance products and ensuring that the ASCO conflict of interest policy is followed through each panel. The disclosures of potential conflicts of interest for the expert panel, including the guests on this episode today, are available online with the publication of the standards in the JCO Oncology Practice, which is linked in the show notes.  So then, to dive into the content of the standards and recommendations. First, Dr. Chan, could you provide both an overview of the scope and purpose of these joint MASCC-ASCO standards and practice recommendations? Dr. Raymond Chan: Thank you, Brittany. First of all, as outlined and introduced by yourself, I would like to acknowledge that this is a great collaboration between the Multinational Association for Supportive Care in Cancer and ASCO. And if you may indulge me for a minute, I would like to give you a little bit of background of how this all started. It was in 2019 when I came across an article written by Ms. Terry Langbaum and Dr. Thomas Smith, who wrote a piece in the New England Journal of Medicine outlining the insufficient work and research done to advance care for people with incurable, long-term, metastatic cancer survivorship. And both Terry and Tom were living with metastatic cancer, and with their lived experience, they provided a new level of meaning to our work. And subsequently, in honor of Terry Langbaum, who is a renowned and esteemed hospital administrator who worked in cancer care, Dr. Thomas Smith and myself created the Terry Langbaum Cancer Survivorship Fellowship and appointed Dr. Nicholas Hart to complete this work.   Within this work, we aim to develop international standards and practice recommendations to guide care for people living with treatable but incurable, metastatic, and advanced cancer. In this work, we conducted an extensive systematic review involving 81 studies, 17 guidelines, and framework documents, gathering the wisdom and consensus from 77 experts from 33 countries around the globe. Together, we reached consensus on 45 recommendations that we hope will be helpful for the clinical care community in improving care, experiences, and outcomes for people living with metastatic cancer. Brittany Harvey: Excellent. Thank you for providing this essential background information and describing the impetus for this project.  Then, as you discussed, Dr. Chan, these standards and recommendations have over 45 recommendations within them. So I'd like to review each of those key points from each section. This document provides these standards and practice recommendations across seven domains. So to start with that first domain, Dr. Chan, what are the key points you'd like to highlight regarding person-centered care?  Dr. Raymond Chan: Sure, Brittany. Now, without repeating what is in the document because I hope that this podcast can lead you to that document and for you to read it in detail, it is really around a comprehensive set of principles that experts felt were important to ensure that patients themselves participate in the care as much as possible. It is around respecting their agency and making sure that their clinical and psychosocial care needs associated with their metastatic cancer diagnosis are considered and addressed.  Brittany Harvey: Absolutely. Thank you for providing those key points regarding person-centered care. So, moving into that next section, coordinated and integrative care, what points would you like to highlight there? Dr. Raymond Chan: Thank you, Brittany, for the question. The standards and recommendations within this section are really around articulating the coordination, navigation, and the multidisciplinary care team approach requirements for this population. In particular for people living with metastatic or advanced cancer, it is not a given that they will be able to access survivorship care services or palliative care services. And a lot of the time, we know that care access is around the resource setting. And a lot of the time, palliative care services may not necessarily be able to cover people living with relatively longer prognosis, such as this population, the longer term metastatic and advanced cancer population. Another point is around transition and the shared care arrangement between the oncology team, survivorship care clinicians where available, and the palliative care team. Once again, these recommendations really articulate the importance of a well-coordinated, integrated approach for these patients. Brittany Harvey: Absolutely. Those points that you just highlighted are important for care for the whole patient.  So then, next, Dr. Nekhlyudov, I'd like to turn to you for the next couple of sections. Could you review what the highlights are for the next section: evidence-based and comprehensive care? Dr. Larissa Nekhlyudov: Yes. Thank you, Brittany. This standard emphasizes that people affected by advanced or metastatic cancer receive the most up-to-date, evidence-based, comprehensive, multidisciplinary, and interprofessional survivorship care and receive it in programs that continuously evolve their approach as guided by evidence. So as such, it is important that these survivorship programs are informed by ongoing professional development, including educational programs for healthcare professionals, that also includes active contributions by those affected by advanced or metastatic cancer. The other piece is that people affected by advanced and metastatic cancer should receive comprehensive care that encourages and supports informed decision-making in order to promote health, manage disease, and reduce stress. Brittany Harvey: Definitely, those are very important points regarding care of the patient.  So then, moving into the fourth domain, Dr. Nekhlyudov, what are the key points for evaluated and communicated care? Dr. Larissa Nekhlyudov: So the famous line is, "What can’t be measured can’t be improved." And so it is important that clinicians routinely and systematically evaluate and monitor supportive care needs and provide appropriate referrals to relevant survivorship care services and healthcare professionals. In order to do that, we need to establish multidirectional communication systems that take into account communication with patients and communication across healthcare professionals involved in their care. Effective communication, of course, needs to be timely, it needs to be clear, effective, respectful, and appropriate. We all know that communication is challenging across cancer care, but it may be particularly so in this specific patient population. For example, in communicating with patients, cancer care clinicians may be comfortable communicating with those with early-stage cancers or patients with early- stage cancers. And may also have had training to communicate with those patients nearing the end of life. But as we already mentioned, those affected by advanced or metastatic cancer may have different needs and as such, it is important that there is additional training for clinicians to address survivorship care needs among these individuals and their caregivers.  And then, in addition to patient-clinician communication, to enable timely communication and collaboration between multiple healthcare providers who may be involved in caring for these patients, enhanced and secure communication strategies are needed. And as with everything else, it's important that healthcare settings engage in service evaluations and quality improvement activities to continue to examine what works, what does not, and make changes that are needed. Brittany Harvey: It is important that these patients with metastatic or advanced cancer have their unique needs met by providing care and appropriate communication to them.  So then, into the next section. Dr. Nekhlyudov, I believe Dr. Chan mentioned this briefly already in talking about being able to access care as part of integrative care. But what is recommended regarding accessible and equitable care? Dr. Larissa Nekhlyudov: Right. Absolutely. I mean, as with any healthcare or cancer care, the standard emphasizes that cancer survivorship care for all people affected by advanced or metastatic cancer is not only comprehensive but also accessible. So affordable, acceptable, available, appropriate, and equitable. And the key is that it does not vary based on someone's personal, cultural, or religious factors. It is important that health workforce diversity and cultural awareness training with the development and provision of culturally and linguistically appropriate resources, that these can help healthcare professionals better understand and cater to the unique needs of the cancer survivor and the caregiver populations. We also need to develop metrics to assess the evaluation  and improvement and make sure that supportive care options are innovative, inclusive, and targeted towards eliminating disparities.  Some of the work that Dr. Chan has otherwise led is looking at provision of telehealth and virtual care for cancer survivors. So particularly for this patient population, it is important to examine the potential benefits of virtual healthcare so that these patients who may have a lot of different needs, physical challenges, mental health challenges, caregivers, that we don’t necessarily bring them to the healthcare setting and can potentially provide them the care that they need. And the last thing that I would like to point out with respect to this is that people affected by advanced or metastatic cancer may face additional challenges particularly returning to work in some capacity and should be supported by advocacy groups, or consumer groups as they are often called internationally, that advocate for accessible and equitable care and then work with specific personnel to access employment, financial and legal assistance that they may need.  Brittany Harvey: Those are important for providing both inclusive and individualized care to every patient who a clinician may see.  So then following those points, what is recommended and what are the key points you’d like to highlight regarding sustainable and resourced care? Dr. Larissa Nekhlyudov: Thanks, Brittany. This is a really important point, and not to take away from any of the other standards, but in order for us to provide ongoing high quality cancer survivorship care for people affected by advanced and metastatic cancer, we need to have a sustainable and adequately resourced approach to do so. So, these standards acknowledge that not all countries or healthcare systems have access to sufficient resources. As such, supportive care may need to utilize a step-care or resource stratified approach that offers the least resource-intensive care that aligns with the needs of the patient, but then also takes into account resources that are available, but really the care should not stop there.  Survivorship care interventions and models of care should be cost-effective yet clinically relevant and meaningful and need to have the adequate financial investment by the healthcare systems. So healthcare settings providing survivorship care for those affected by advanced and metastatic cancer have to be properly resourced in order to provide high quality ongoing care. And this includes intentional planning for support services, and  where healthcare settings provide these programs with adequate level of human resources, equipment, facilities, and leadership who value support, facilitate, and appropriately invest in such care. And as we mentioned before, it’s always important to continue to evaluate what is being provided, what is being offered, sort of what are the return on investment metrics in order to continue to evolve the programs to serve the needs of the population.  Brittany Harvey: Understood. I appreciate you providing highlights across these past couple of domains. So then to turn to the last domain, Dr. Chan, what is recommended regarding research and data-driven care? Dr. Raymond Chan: So the panel actively advocated for cancer registries to enable population-wide surveillance of the incidence and prevalence of people with advanced or metastatic cancer. Knowing the number of people with advanced or metastatic cancer is extremely important for care planning. We also advocated for the active involvement of people affected by advanced or metastatic cancer to participate in the co-design of research so that we can make sure that our research better meets the needs or end-users and enhance the rigor, relevance, reach, and impact of survivorship research.  The last point I would like to highlight is that a number of survivorship trials out there only limit the population or the focus of the trial being on early stage disease, people treated with curative intent. And within this standards and principles, we advocated for research trials to explicitly include people affected by advanced or metastatic cancer in the clinical trials and trying to address also the barriers that impede people from enrolling or participating at all levels.  Brittany Harvey: Thank you both for reviewing these key points, standards, and practice recommendations across these seven domains.   These standards and recommendations cut really across all aspects of care for people impacted by advanced and metastatic cancer. Dr. Nekhlyudov, in your view, what is the importance of these standards and how they will impact clinicians? Dr. Larissa Nekhlyudov: Thank you for that question, Brittany. The MASCC-ASCO standards were developed, as we already mentioned, to promote the provision of high-quality, evidence-based survivorship care for people with advanced or metastatic cancer emphasizing the need for care that is person-centered, coordinated and integrated, evidence-based and comprehensive, evaluated, and communicated, accessible and equitable, sustainable and resourced, as well as research and data-driven. For clinicians, these standards and practice recommendations provide a critical resource in order to facilitate tailored and effective care for people living with advanced or metastatic cancer across disciplines and settings.  As we know, and much of it is due to the efforts of ASCO, cancer care is always changing resulting in changing prognoses. As such, people diagnosed with cancer in the past that had poor prognosis are now living and are living longer. And so diagnoses that fall into this specific category of patients that we’re discussing here today will continue to evolve. And likewise, advanced cancer is less clearly defined for other cancer such as hematologic or CNS malignancies, but these survivors may face similar issues and challenges.   So overall, applying these standards will help provide survivorship care to these patients. And the important piece is that what we hoped to achieve with these standards is that when we consider survivorship care, we are not only applying it to those who have early stage disease. We’re not applying it only to those whose disease has been “cured.” We’re not applying it to those who have been deemed disease-free or those who have completed treatments. We really need to make sure that clinicians understand the challenges experienced by often disregarded or forgotten population of cancer survivors and yet acknowledge the ever changing landscape of cancer survivors and appropriately apply these survivorship standards for people affected by advanced or metastatic cancer. And I think as Ray would probably say as well, we should focus on including rather than excluding people with cancer, all cancers, from survivorship services and programs.  Brittany Harvey: Definitely. This is an important population with often unrecognized or unmet needs, and the goal of these standards, as you’ve mentioned, is to provide a better quality survivorship care for patients with advanced and metastatic cancer.   So that leads nicely into my final question for you, Dr. Chan. In your view, how do these standards and recommendations impact people affected by advanced or metastatic cancer? Dr. Raymond Chan: As we continue to promulgate these standards of recommendations, I believe that patients will benefit from these standards in three ways.  First, as clinicians, researchers, and service planners continue to improve care as per outlining the standards, patients are going to indirectly benefit from it. It is meant to lead to better care, better experiences, and better outcomes.  Secondly, it is around the expectations of care. Many of us here would know that if we don’t expect that care, it is unlikely that we would go and try to access it. And so it is extremely important that patients know what to expect. So now that I have been diagnosed with advanced or metastatic cancer, what does good care look like? So in the past, there are a number of pallaiative care standards whereby people are thinking, “Do I need palliative care? What does good palliative care look like?” Their set of standards. And now, these standards would enable patients to develop that expectation around what good care looks like.  Thirdly is around the patients, the family units, and their navigators or their care networks to advocate for themselves, to advocate for the patient, to be able to access that care from the care team. So we hope that as we continue to promulgate these standards, that benefit would be translated into the real world for people affected by advanced or metastatic cancer. Brittany Harvey: Excellent. We definitely hope that this improves care for all patients impacted by advanced and metastatic cancer.   So, I want to thank you both so much for this important work to develop these recommendations and standards. And thank you for taking the time to speak with me today, Dr. Nekhlyudov and Dr. Chan.   Dr. Larissa Nekhlyudov: Thank you. Great to be here.   Dr. Raymond Chan: Thank you.   Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full standards and practice recommendations, go to www.asco.org/standards. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.  The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Dr. John Gordan discusses the newest evidence-based guideline update from ASCO on systemic therapy for advanced hepatocellular carcinoma (HCC). He shares the updated recommendations for first-, second-, and third-line therapy for patients with Child-Pugh Class A liver disease, guidance for patients with Child-Pugh Class B liver disease. Dr. Gordan also touches on the importance of this guideline for both clinicians and patients and the outstanding questions regarding treatment options for HCC. Read the full guideline, “Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update” at www.asco.org/gastrointestinal-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/gastrointestinal-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.02745   Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.  My name is Brittany Harvey, and today I'm interviewing Dr. John Gordon from the University of California, San Francisco, lead author on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update." Thank you for being here, Dr. Gordon. Dr. John Gordon: Of course, happy to be here. Brittany Harvey: Before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Gordon, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.   So, to jump into the content of this episode, first, Dr. Gordon, what prompted this update to the Systemic Therapy for Advanced Hepatocellular Carcinoma Guideline, which was last published in 2020?  Dr. John Gordon: So, both the initial guideline in 2020 and then the update now were driven by advances in the standard of care. The original 2020 guideline was actually held for a little bit so that we could incorporate the availability of atezolizumab plus bevacizumab, which just reported back and then received FDA approval during 2020. We were happy to be able to provide what was a very timely update to clinicians about being able to use that new regimen that had really changed the face of therapeutics for advanced HCC. The update was driven again by a shift in therapeutics, specifically it was the presence of much more evidence for the use of combination CTLA-4, PD-1 or PD-L1 immunotherapy strategies. The primary thing was the availability of durvalumab plus tremelimumab, which was studied in the so-called HIMALAYA phase III trial. The key shift in this guideline was being able to incorporate those data as a second first-line option. Furthermore, when the 2020 guideline was released, data were just becoming available about the combination of ipilimumab and nivolumab, and were not covered in any great detail. So we wanted to be able to be sure to incorporate both of those regimens, which we thought were quite significant in the current therapy for advanced HCC. Brittany Harvey: Appreciate you providing that background on the evidence informing both the original guideline and this update. Next, I'd like to review the key recommendations of this update. So, starting with, what is recommended for first-line therapy? Dr. John Gordon: The current recommendation in the first-line setting is to offer patients either atezolizumab plus bevacizumab, sometimes called atezo-bev or durvalumab plus tremelimumab. But, at this time, those two regimens we’re not able to distinguish between them based on the primary evidence available. But there are a few distinctions in the studies and the patients that physicians may wish to consider. In particular, because atezo plus bev contains an immune therapy and then an anti vascular agent, for patients who are not eligible for antivascular agents or for whom an antivascular therapy might be of higher risk, for example, people with a history of esophageal varices or people with peripheral arterial disease, we would encourage physicians to preferentially consider durva plus treme.  Similarly, for patients where reactivation of an autoimmune disorder is a particular concern, staying away from the more potent immune combination is also advised. But again, the data themselves support the consideration of both, and it's really up to the provider, their multidisciplinary team, and then communication with the patient to determine what is optimal for that patient.   In addition, in the frontline setting, it is advised that for those patients who are unable to receive atezo plus bev or durva plus treme, sorafenib and lenvatinib, the traditional tyrosine kinase inhibitors that were more commonly used prior to 2020, may also be considered in the frontline setting. Furthermore, for some patients, it's also reasonable to consider the use of durvalumab alone, which is the PD-L1 inhibitor component of the durva-treme combination.  Brittany Harvey: Understood. It’s helpful to understand which regimens are optimal for which patient population and options that are available for shared decision making between patients and their clinicians.  So then, following those recommendations for first-line treatment, what is recommended for second-line therapy? Dr. John Gordon: One of the things I want to be clear about the second-line recommendations is that these are largely driven by expert opinion rather than primary research studying the use of these agents after either atezo plus bev or durva plus treme. So, if you look at the history of HCC drug development, five or ten years ago, when we were confined to the use of sorafenib in the frontline setting, many studies explicitly studied the second and later-line population. But in the current era, where new frontline therapies have supplanted those agents, it becomes a little bit harder to provide a truly evidence-based answer. As a result, the recommendation is, frankly, to consider all of the options of FDA-approved agents and just as was the case of the frontline setting, to balance what might be patient-specific characteristics, both in terms of comorbidities and also ability to adhere with these regimens, which are not the easiest. All of those things should be considered when opting for a second-line agent.  Just to be slightly more explicit about it, for those patients who've received frontline atezo-bev, the considerations would be either transitioning to a tyrosine kinase inhibitor, most classically sorafenib, lenvatinib, or cabozantinib, or in principle, ramucirumab, the biologic antivascular agent, or a CTLA-4 and PD-1 or PD-L1 combination, such as durva-treme or nivolumab plus ipilimumab. Conversely, for those patients who might have received durva-treme in the frontline setting, it's reasonable to consider either a TKI or atezo plus bev. Brittany Harvey: Absolutely. Thank you for reviewing both those recommendations and the level of evidence behind those. I think it's important that even in areas where the expert panel didn't have a lot of evidence to go off of, there are still recommendations available for clinicians that are based on expert opinion.  So then, following those second-line therapy options that you just described, what recommendations did the expert panel make for third-line therapy? Dr. John Gordon: So, regarding the recommendation for third-line therapy, one of the things that we did want to make clear as a panel is that third-line therapy is a reasonable consideration in a subset of HCC patients. Quite often, five or ten years ago, it was very seldom that a patient might be considered for frontline therapy because of the burden of toxicity and/or disease progression during the first two lines. But now, for patients with intact liver function and good performance status, I think it's very reasonable to consider the same list of agents that might have been considered for second line. And again, I think the general guidance here is if you've already given your patient both atezo-bev and some kind of CTLA-4 and PD-1 combination, it's probably best to use a non-overlapping regimen, something like a TKI. If, in the frontline setting, you followed atezo-bev by TKI or durva-treme by TKI, then it would be reasonable to look at the immune therapy combination that the patient hadn't received yet. Unfortunately, again, at this point, this is all at the level of expert guidance and personal experience. But just thinking about the mechanistic rationale behind these different combinations, and which ones your patient has had the opportunity to benefit from yet, is probably the best guidance that we can give as you move into the later line. Brittany Harvey: Definitely. Thank you for reviewing that guidance as well.  So then, these recommendations that you've already described refer to patients with Child-Pugh Class A liver disease. What is recommended in the guideline for patients with Child-Pugh Class B advanced hepatocellular carcinoma? Dr. John Gordon: Thanks. I think that's another important question, and it's a part of the field that's still evolving. So this is in some ways similar to the situation for third line therapy. The level one evidence that we have and the clinical trials that were done were almost exclusively done in the context of Child-Pugh A liver function. But we know well that many patients with hepatocellular carcinoma have some degree of impairment to their liver function, making them Child-Pugh Class B or beyond. Similar to third line therapy, we do believe that it's appropriate to cautiously consider systemic therapy for these patients, particularly a better compensated patient with Child-Pugh Class B liver function may be considered. The same systemic therapy options that are considered for patients with Child-Pugh Class A may be considered here, even to the level of considering atezo-bev or durva plus treme. I will also acknowledge, though, that when considering the liver function, bleeding risk, portal hypertension, and all of the other issues that may be at play, it may end up being safer for clinicians to consider monotherapy with an agent like durvalumab or using a TKI, by simple virtue of the fact that if complications ensue, treatment can be interrupted and the therapeutic will leave the patient's system relatively promptly. The key take home here is please do consider systemic therapy in this population, but also consider it with caution, with an understanding that the underlying hepatic dysfunction also plays a role in considering and affecting the outcome. Brittany Harvey: Thank you for reviewing those recommendations for patients with Child-Pugh Class B advanced HCC and all of these recommendations, which are based off of expert review of the evidence and consensus of the entire expert panel.  So then, Dr. Gordon, in your view, what is the importance of this guideline update, and how will it impact both clinicians and patients with hepatocellular carcinoma? Dr. John Gordon: I think the impact of this guideline update was really to open the field and really just make clear that the use of CTLA 4-containing combinations was appropriate for patients with HCC because those data were not available at the time of the last guideline and to try to provide some insight about where and when to incorporate them. We really think that these agents have the potential to significantly impact outcomes for patients with HCC, and so we wanted to be clear that these can be considered therapeutically even after frontline use of a PD-L1 inhibitor like atezolizumab. And so I think the key objective of this guideline is really to be enabling and really to make it clear that within the now somewhat surprisingly broad range of approved agents that we have for HCC, these options are on the table and may be used in succession, depending on patient-specific tolerance and their clinical course.  Brittany Harvey: Absolutely. So then you've specifically mentioned that both the original guideline and the guideline update were developed to provide timely guidance from recently published randomized clinical trials. So what are the outstanding questions still regarding treatment options for advanced hepatocellular carcinoma?  Dr. John Gordon: I think those questions are really reflected in one of the things which is challenging about these guidelines, which is that it's a very kind of open set of guidelines. We provide clinicians with a range of options, but we're really not in a position to provide much evidence-based guidance around treatment selection beyond the sort of careful avoidance of contraindications. I think that there will continue to be drug development for HCC. I think there are more potent immune therapies that are currently in use for other tumors that are being studied here, and I think we do hope to see new agents in future guidelines as well. But I really feel like the key question is going to be starting to stratify patients for who's going to be most likely to benefit from exposure to an antivascular agent, who's going to be more likely to benefit from exposure to a more potent immunotherapy so that we can give our patients the best medicine for them in the first setting, and that we're less in the position of having to sample the available options to see which one might work for our patient. And I think that's going to require significant effort, particularly, honestly, in academic medicine, as these medicines start to get used, to develop the kinds of data that will enable identification of biomarkers and mechanisms of response, as well as identification of efficacy, which has been this sort of key limiting step in HCC therapeutics for the last 10 years. Now that we've got so many effective agents, we would like to see them be more effective, but nevertheless, it's been huge strides forward. Then the question is, who gets what when?  I think the other place of interesting development right now is the integration of locoregional therapies like embolization procedures, either chemoembolization or radioembolization, as well as stereotactic body radiotherapy with systemic therapy. My suspicion is that it's going to take a little bit more time before the use of these is really well understood and how they might fit into the current standards of care. But we're starting to see some large studies tackling this question. I think that we will see impact of the combinations of systemic therapy and local regional therapy in guidelines to come in parallel to a better understanding of which treatment is right for which patient. Brittany Harvey: We'll look forward to all of the future developments in the care of patients with advanced hepatocellular carcinoma, and look forward to inclusion of all of the things that you just mentioned into guidelines in the future.  So I want to thank you, Dr. Gordon, for all of your work that you've done to update these guidelines and for taking the time to speak with me today.  Dr. John Gordon: Absolutely. And I actually just want to express what a great experience I've had working with the ASCO Guidelines team. I think that this is very challenging work, and I really appreciate the professionalism and commitment that they bring to it. I think it has a huge impact, and I'm glad to be part of it. Brittany Harvey: Absolutely. And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Dr. Lisa Law and Dr. Randy Taplitz share the latest evidence-based recommendations from ASCO on vaccines in adults with cancer. They discuss recommended routine preventative vaccinations, additional vaccinations and revaccinations for adults undergoing HSCT, CD19 CAR-T treatment, or B cell-depleting therapy, guidance for adults with cancer traveling outside the U.S., and recommendations for vaccination of household and close contacts of adults with cancer. Dr. Law and Dr. Taplitz also share their insights on the guideline, including the importance of this guideline for adults with cancer and their clinicians, future advances in research, and current unmet needs. Read the full guideline, “Vaccination of Adults with Cancer: ASCO Guideline” at www.asco.org/supportive-care-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/supportive-care-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00032       The ASCO Specialty Societies Advancing Adult Immunization (SSAAI) Project is supported by the Centers for Disease Control and Prevention (CDC) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award to the Council of Medical Specialty Societies (CMSS) (with 100 percent funded by CDC/HHS). The contents are those of the authors and do not necessarily represent the official views of nor endorsement, by CDC/HHS or the U.S. Government. Brittany Harvey: Hello, and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.  My name is Brittany Harvey, and today, I am interviewing Dr. Lisa Law from Kaiser Permanente and Dr. Randy Taplitz from City of Hope Comprehensive Cancer Center, authors on “Vaccination of Adults with Cancer: ASCO Guideline.” Thank you for being here, Dr. Law and Dr. Taplitz. Dr. Lisa Law: Thank you. Dr. Taplitz: Thank you, Brittany. Brittany Harvey: Before we discuss this guideline, I'd like to take note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Taplitz and Dr. Law, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to dive into the content, here first, Dr. Taplitz, can you provide a general overview of both the scope and purpose of this guideline on vaccination of adults with cancer? Dr. Randy Taplitz: Yes, so people with cancer often experience a compromised immune system due to a variety of factors. This includes chronic inflammation, impaired or decreased function of the hematopoietic system, and treatments that compromise their immune function. Because of this, people with cancer are at a higher risk for infection, including with vaccine-preventable diseases. Also, response to vaccines in patients with cancer may well be affected by this underlying immune status, and their anticancer therapy, as well as the severity of the underlying malignancy. The purpose of vaccination in this group of patients is to prevent infection or to attenuate the severity of the disease when infection cannot be fully prevented.   This ASCO review builds on a 2013 guideline by the Infectious Diseases Society of America, or IDSA, and uses what’s called a systematic literature review of 102 publications between 2013 and 2023. This includes 24 systematic reviews, 14 randomized clinical trials, and 64 non-randomized studies. The largest body of evidence in these studies, not surprisingly, addresses COVID vaccines on the efficacy and safety of vaccines used by adults with cancer or their household contacts. ASCO convened an expert panel to review this evidence and formulate recommendations for vaccinations in this population. Brittany Harvey: Understood. I appreciate that context, Dr. Taplitz. So then, next, Dr. Law, I'd like to review the key recommendations of this guideline. The guideline addresses four overarching clinical questions. So starting with the first question, what are the recommended routine preventative vaccinations for adults with cancer? Dr. Lisa Law: Thank you, Brittany. Before I start, I just want to wholeheartedly thank the first author of this paper, Dr. Mini Kamboj, Dr. Elise Kohn from the NCI, as well as the ASCO staff in putting this publication and guideline together. It is a very, very important guideline, and I echo everything Dr. Taplitz just said.  So going back to your question, what are the recommended routine preventative vaccines for adults with cancer? As per this guideline, there are about 7 to 8 based on patient age and risk. Namely, they are: seasonal flu, RSV for those aged 60 or above, COVID-19, Tdap, Hepatitis B, Shingrix, Pneumococcal vaccine, and the HPV vaccine. These vaccines should ideally be given two to four weeks before therapy. However, non-live vaccines can be given anytime during or after chemo, immunotherapy, hormonal treatment, radiation, or surgery. Brittany Harvey: Excellent. Thank you for reviewing those vaccinations and the timing of them as well. So then, following those recommendations, Dr. Taplitz, what additional vaccinations and revaccinations are recommended for adults undergoing hematopoietic stem cell transplantation, CD19 CAR-T treatment, or B-cell depleting therapy?  Dr. Randy Taplitz: Many studies have shown that stem cell transplant recipients essentially lose immunity from childhood immunizations, and we know that these individuals are very vulnerable to infection, particularly in the first year after transplant. Revaccination is critical to help restore their immunity. The optimal timing of vaccination is based on our understanding of adequate immune reconstitution with B and T-cell recovery so that the individual can mount a response to the vaccine. We know that a lot of factors influence this immune reconstitution, including the age of the stem cell transplant recipient, the source of the donor, the time from transplant, graft-versus-host disease prophylaxis, the treatment and severity of graft-versus-host disease, and the vaccine type and antigens used.   There are a number of bodies throughout the world, IDSA as I mentioned, CDC, American Society for Transplant and Cellular Therapy, European Society for Blood and Marrow Transplant, and European Conference for Infections and Leukemia. All of these bodies have guidelines that approach vaccination in stem cell transplants. However, variation does exist in the use of a variety of things including whether to use immune predictors to help guide vaccination, and there is really not consensus on whether this immune predictor guided vaccination is more likely to produce a protective immune response versus a standardized schedule. In addition, the duration of protection is incompletely understood.  The bottom line in these guidelines is that they recommend complete revaccination starting for most vaccines at 6 to 12 months after stem cell transplant, in order to restore vaccine-induced immunity. And I just want to go through a few of the particulars. For COVID-19, which is a three-dose series in the primary series, influenza - generally high-dose influenza - and pneumococcal vaccine, PCV20 in general, ultimately four doses, can be administered, starting as early as three months after transplant. Although there is really not much data to guide the use of the recombinant zoster vaccine in allogeneic stem cell transplant, the vaccine can be administered after the end of antiviral prophylaxis, which in general is 12 to 18 months after allogeneic and 3 to 12 months after autologous stem cell transplant. Some of the other vaccines, such as hepatitis B, Tdap, meningococcal vaccines, and HPV revaccination in those less than 45 are also recommended.   I want to also spend the moment talking about the two recently licensed RSV vaccines, which were essentially studied in less compromised hosts and really without any immunogenicity data in stem cell transplant, and thus, there is no recommendation in this guideline for the use of these vaccines after transplant. Live vaccines, such as MMR and varicella – varicella would be in varicella-seronegative patients without a prior history of varicella – should be delayed for at least two years and only given in the absence of active graft-versus-host disease or immunosuppression.  Moving briefly to CAR T, which is an immunotherapy that involves adoptive cell therapy, given the available data and after a review by the group, it was recommended that adults with hematopoietic malignancies receiving CAR T therapy directed against B-cell antigens should receive influenza and COVID-19 vaccines either two weeks before lymphodepletion or no sooner than three months after the completion of therapy. Administration of non-live vaccines preferably should occur before CAR T treatment or at least 6 to 12 months after, following the same timing as what we recommend for stem cell transplant. There is really little data to guide the safety and timing of administration of live vaccines after CAR T therapy.   In terms of adults receiving B-cell depleting therapy, they are generally unable for time to mount an effective humoral response but may have at least partially intact cellular immune responses. They are encouraged to be revaccinated for COVID-19 no sooner than six months after completion of B-cell depleting therapy, and they should receive influenza vaccine approximately four weeks from the most recent treatment dose for patients on chronic therapy. For other non-seasonal immunizations, vaccines ideally should be given two to four weeks before commencing anti-CD20 therapy or delayed until 6 to 12 months after completion, except for the recombinant zoster vaccine, which can be given one month after the most recent dose of B-cell depleting therapy. Brittany Harvey: I appreciate you reviewing each of those vaccinations and when they should be given, and reviewing the available data – albeit, limited data – in these situations.  So beyond these routine preventative vaccinations and revaccinations that you've both just described, Dr. Law, what additional vaccinations does the expert panel recommend for adults with cancer traveling outside the United States? Dr. Lisa Law: Good question. As per these ASCO guidelines, adults with solid or blood cancer traveling outside of the United States should follow the CDC standard recommendations for their destination. For the 2024 CDC Yellow Book, travel vaccines, in general, should be delayed until three months from the last chemotherapy or, and for those with solid tumors, ideally when the disease is in remission. Of note, hepatitis A, typhoid, inactivated polio, Hep B, rabies, meningococcal vaccine, and Japanese encephalitis vaccines are considered to be safe. In all cases of travel, patients should be counseled by their healthcare provider about the travel timing, with the additional attention to the regional seasonality of infections, for instance, influenza is more common in late summer in Australia, and also with attention to any outbreaks that may be occurring globally at the time of travel. Brittany Harvey: Absolutely. Those are key points for clinicians to discuss with their patients as they consider upcoming travel.  So then, the final clinical question that the panel addressed, Dr. Taplitz, what vaccinations does the panel recommend for household and close contacts of adults with cancer?  Dr. Randy Taplitz: Thank you. Yes, it is recommended that all household members and close contacts, when possible, be up to date on their vaccinations. And the only further thing I would say is that there are some special considerations for the use of live vaccines in household contacts, particularly in stem cell transplant recipients. Contacts of people who receive stem cell transplants should preferably receive inactivated influenza vaccines. As was mentioned, MMR and varicella vaccines are both safe to administer to close contacts. Vaccine strain transmission to immunocompromised hosts has not been associated with MMR use in family members.   Eleven cases of the varicella vaccine strain transmission are described in the published literature, but none occurred in compromised hosts. Because the vaccine strain can cause severe and fatal varicella in profoundly immunocompromised people, precautions are advised to avoid close contact with a person with a vaccine-induced rash. For household contact travelers, MMR and yellow fever vaccines are considered safe. Oral cholera should be avoided. For smallpox vaccines, the second-generation ACAM2000 has rarely been associated with vaccinia transmission and should be avoided because of this. But the live replication-deficient MVA-based JYNNEOS vaccine is felt to be safe for household contacts of immunocompromised individuals. Brittany Harvey: I appreciate you reviewing the importance of vaccination for household and close contacts, and some of those precautions that individuals should take. I appreciate you both for reviewing all of these recommendations.  So then in your view, Dr. Law, what is the importance of this guideline, and how will it impact both clinicians and adults with cancer? Dr. Lisa Law: In my opinion, this is a very important guideline that is long overdue in the oncology community and will have a huge impact on both clinicians and adults with cancer. Over the years, I have often been asked by my colleagues and patients, “Can I have the flu vaccine, and if so, when?” So this guideline really is going to be helpful. More importantly, our cancer patients are living much longer. They may have years of quality of life even with third or fourth line of treatment, especially, for instance, like CAR T for myeloma and lymphoma. However, we know that with additional treatment, that carries a substantial risk of infection complication among these immunocompromised patients. So it is of paramount importance to inform our patients and colleagues to be proactive in advocating preventive therapy ahead of time, meaning trying to get the patients appropriately vaccinated as early as possible to generate immunity.  Another case in point is the Shingrix vaccine. I used to see lots of shingles, but ever since we have the recombinant Shingrix, I have fewer encounters. And this is huge because post-herpetic neuralgia robs a patient’s quality of life. So, again, it is very important to recommend appropriate vaccines for our cancer patients.  Brittany Harvey: Absolutely. It is key to ensure patients receive these preventative vaccines, and we hope that this guideline puts an emphasis on that for clinicians and patients.  So finally, to wrap us up, Dr. Taplitz, what are the current gaps in knowledge regarding the vaccination of people with cancer? Dr. Randy Taplitz: There are a number of really important gaps in knowledge and really critical unmet needs that require research and other dedicated efforts. Among these are, and I think paramount, are really the participation of people with cancer with varied types of immunocompromise in vaccine trials. Where vaccine trials are only for cancer patients, obviously is ideal, testing vaccines in the appropriate population. But when that's not feasible, pre-existing cancer should not preclude eligibility, and inclusion of cohorts of people receiving anticancer treatment should be incorporated prospectively. So that’s really critical because the quality of our guidelines is based upon the data. We use the data for developing guidelines and gathering more data in the particular patient population is really, really critical.  Secondly, work for creating more immunogenic vaccines and research to understand the immune response to vaccines after immuno-depleting therapies, particularly with newer therapies such as CAR T and newer B cell therapies, bispecific antibodies, etc. is really critical. We need to really understand the immune response and have the most potent vaccines available to these people who may have impaired immune responses.  Switching gears a little bit, we really need mechanisms to promote institutional commitment to integrate and sustain immunization best practices for people with cancer. This will largely be through multidisciplinary, team-based approaches, protocol-based vaccination standing orders, and leveraging data sharing so that we can all be on the same page with giving vaccines to these individuals. We also need education and evidence-based decision-making tools, emphasizing preventive care through immunization, the availability of educational resources to clinicians and patients to address commonly asked questions and also misconceptions about vaccination, that’s absolutely critical.  And finally, I think we need to develop strategies for addressing unique challenges and factors contributing to vaccine hesitancy during cancer therapy. We need to focus on patient and clinician communication, and very importantly, we need to consider health equity considerations in the development and approach to vaccines in these compromised patients. Brittany Harvey: Definitely, we'll look forward to research and advances in these areas that you've just described to support these guidelines and increase vaccine uptake.  So I want to thank you both so much for your work on this important guideline, and thank you for your time today, Dr. Law and Dr. Taplitz. Dr. Lisa Law: Thank you.  Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

Dr. Ilana Braun and Dr. Eric Roeland join us on the ASCO Guidelines podcast to discuss the latest evidence-based recommendations on cannabis and cannabinoids in adults with cancer. They discuss nonjudgmental patient-clinician communication, the relatively narrow cancer-related indications for which there is actionable clinical evidence for cannabis and/or cannabinoids, and key information for adults with cancer and their clinicians. Dr. Braun and Dr. Roeland also review the limited evidence regarding cannabis and cannabinoid use in adults with cancer and the outstanding questions and importance of research in this area. Read the full guideline, “Cannabis and Cannabinoids in Adults with Cancer: ASCO Guideline” at www.asco.org/supportive-care-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/supportive-care-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcast hosts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all of the shows, including this one, at asco.org/podcasts.  My name is Brittany Harvey, and today, I’m interviewing Dr. Ilana Braun from Dana-Farber Cancer Institute, and Dr. Eric Roeland from Oregon Health & Science University, co-chairs on “Cannabis and Cannabinoids in Adults with Cancer: ASCO Guideline.”   Thank you both for being here Dr. Braun and Dr. Roeland. Dr. Ilana Braun: Thanks so much for having us, Brittany. Dr. Eric Roeland: Thanks, Brittany. Brittany Harvey: Then, just before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensures that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Braun and Dr. Roeland, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. Then to jump into the content of this guideline, first, Dr. Roeland, could you give us an overview of both the scope and purpose of this guideline?  Dr. Eric Roeland: Sure, Brittany. I think it's important for everyone to recognize just how common the issue of cannabis or cannabinoid use is amongst people living with cancer. And I think clinicians in academia as well as through community sites, we are asked about the use of cannabis on a daily basis. And so our target audience is really to focus on clinicians providing care to adults with cancer, but also the health systems in which we work because this is a very complex issue, as well as the people living with cancer and their caregivers, as well as researchers dedicated to this field. Brittany Harvey: So as you mentioned, this is a complex issue, and I'd like to review the key recommendations of this guideline. This guideline provides recommendations across three clinical questions that the expert panel targeted. So, starting with the first question, what is recommended for patient-clinician communication regarding cannabis or cannabinoids?  Dr. Ilana Braun: Given the high prevalence of medicating with cannabis or cannabinoids that Eric references, somewhere in the neighborhood of 20% to over 40% of adults with cancer consume cannabis products, ASCO's guideline offers the following common-sense, good practice statement: In the clinic, providers should routinely and non-judgmentally inquire about cannabis consumption or consideration of cannabis, and either guide care or direct adults with cancer to appropriate resources. In other words, the guideline works to fully destigmatize this conversation. The guideline goes on to offer suggestions for taking a cannabinoid and cannabis history. This includes the goals of use, how the products are sourced, what formulations are being used (including the ratios of active ingredients like THC and CBD), the inactive ingredients (for instance coconut oil), whether it is herbal or synthetic, and whether the product is pharmaceutical grade or non-pharmaceutical grade. And then other questions like routes of administration, dosing schedules, perceived benefits and risks, and whether the products are being used adjunctively or as a replacement for standard treatments. It is also probably important to query potential contraindications, such as a history of cannabis use disorder or psychosis.  Brittany Harvey: Thank you for reviewing those good practice statements. Those are key for non-judgmental communication and taking an accurate and complete history.  So following those statements, the expert panel next addressed the question: Does use of cannabis and/or cannabinoids by adults improve cancer-directed treatment? What recommendations did the expert panel provide for this section? Dr. Eric Roeland: When we think about the use of cannabis or cannabinoids in treating the underlying cancer, it's incredibly important to recognize the excitement that patients and clinicians have around the potential promise. Much of this data is generated from preclinical models. However, when we're engaging patients consuming cannabis or cannabinoids to augment their cancer-directed treatment, we could find no evidence to support its use. And so we do not recommend that patients be using it to augment treatment, nor do we recommend that patients should be using it instead of their cancer-directed therapy. And I think this is a major challenge for multiple oncologists, where their patients may be using these with a goal of treating their cancer, and then present with very advanced cancer and/or multiple poorly controlled symptoms. Dr. Ilana Braun: And I think that there are some areas of particular concern. For instance, there were two oncologic cohort studies that suggest that cannabis, which we know is an immune modulator, may actually worsen immunotherapy outcomes. These outcomes included median time to progression and overall survival. There are obvious limitations of preliminary observational data, and we now need to gather prospective, gold-standard data. But for the time being, the guideline recommends that clinicians should advise against adults receiving immunotherapy from medicating or considering medicating with cannabis and cannabinoids. And then I think there are some additional reasons for concern. First of all, this type of therapy tends to be very expensive and not covered by insurance and there are some risks for drug-drug interactions, in terms of pharmacodynamic ones, Cannabis may exacerbate neuropsychiatric side effects of opioids and even benzodiazepines. In terms of pharmacokinetic drug-drug interactions, it's not a particularly risky substance, but there are three to be wary of in particular: warfarin, buprenorphine, and tacrolimus all have high-risk interactions with cannabinoid products.  Brittany Harvey: I appreciate you both for reviewing these recommendations and evidence regarding the use of cannabis and/or cannabinoids regarding cancer-directed treatment.   So then the last clinical question, Dr. Braun, what is recommended regarding use of cannabis and/or cannabinoids in managing cancer treatment-related toxicities and/or symptoms? Dr. Ilana Braun: The first thing to make clear is that high-quality clinical evidence evaluating the utility of cannabis and cannabinoids for adults with cancer is limited as Eric has said. The evidence that does exist weakly supports a practice of using cannabis and cannabinoids to address refractory chemotherapy-induced nausea and vomiting when standard treatments have failed. For other potential oncologic indications, like management of cancer-related pain, there is weak, negative, conflicting, or no evidence. But that being said, a 2017 monograph published by the National Academies of Science, Engineering, and Medicine concluded that there is substantial evidence that cannabis is an effective treatment for chronic non-cancer pain, and I’m sad to say, that chronic non-cancer pain happens too in adults with cancer. Brittany Harvey: Thank you for reviewing those recommendations as well.  So you've both touched on this a little bit in that patients are often asking clinicians for recommendations regarding cannabis and/or cannabinoids, but in your view, what is the importance of this guideline, and what should clinicians know as they discuss these recommendations with their patients? Dr. Eric Roeland: Probably one of the most important points is for clinicians to ask and to be open and to create a space where our patients are telling us about what they're using. I think we've all had patients that we’ve been surprised that have been using cannabis or cannabinoids in conjunction with other medications that may increase the risk of unwanted side effects or risks, including sedation or falls. I also find it challenging that many patients are receiving recommendations for the use of cannabis or cannabinoids directly from friends or family instead of through their medical providers. Therefore, I think one of the very first things is to just make sure that you’re asking about it and then inquiring what the goal of their use is.  When we talk about the use of cannabis, we also need to recognize the difference between the available data that can guide us in evidence-based recommendations, as well as the enthusiasm and available access that patients have to cannabis that has really outpaced our ability to research it. So it's important to recognize these tensions that we're living with in clinic day-to-day. Brittany Harvey: Absolutely. Those points are key for clinicians as they discuss this complex issue with their patients.  Following that, how will these guideline recommendations affect adults with cancer? Dr. Ilana Braun: One really important takeaway from these guidelines is that they clearly state that cannabis and cannabinoids are medicinal, and for a medical community to clearly articulate this point is notable. I suspect they will provide encouragement, legitimacy, confidence, and even a script to oncology clinicians who were previously reticent to inquire, document, and provide clinical recommendations around non-pharmaceutical cannabis and cannabinoids. It may have a similar effect even at the institutional level in terms of supporting these practices. At the same time, I suspect they will encourage those who are recommending oncologic use of cannabinoids and cannabis for myriad cancer-related indications to adopt a more circumscribed approach. The reason I say this is that the cancer-related indications for which there is actionable clinical evidence at this time are quite narrow. So all this to say, I believe these guidelines will lead to greater transparency around cannabis decision-making in the clinic, as Eric mentions, but also lead to a possible narrowing of indications for which cannabis is clinically recommended.  Dr. Eric Roeland: Another major role of the use of these guidelines in clinical care is informing clinicians and patients about cannabis. Cannabis has been used by humans as a plant for thousands of years, and although it's a very complex plant with hundreds of parts, the two parts that researchers have studied most are delta nine-tetrahydrocannabinol, or THC, and cannabidiol, or CBD. In rough terms, THC can cause a high feeling, while CBD typically does not. And there are multiple types of products that have different ratios of THC and CBD. So it's critical for people to understand what those ratios are, how many milligrams of those things there are, as well as what are the programs within your region to measure or quantify what's actually in the products you're consuming. If a person with cancer medicates with cannabis, most oncologists would prefer that they use it by mouth, such as an edible, rather than inhaling or smoking cannabis given concerns about potential impact on lung function. One challenge when consuming cannabis by mouth is that it can take up to two hours to have its full effect. So patients should be very careful not to take too much or to stack their doses, which can cause sedation, confusion, and even increase the risk of falls. Whereas when patients are consuming cannabis by breathing in a smoke or vapor, they typically feel the effects almost right away, which is why patients sometimes prefer smoking or vaping as their preferred route of administration. Brittany Harvey: Understood. Definitely. We hope these guidelines provide key information and clarity for both adults with cancer and their clinicians.  So then, finally, you've both mentioned that there is limited evidence regarding cannabis and cannabinoid use in adults with cancer. So what are some of the outstanding questions regarding cannabis and cannabinoids in cancer care? Dr. Eric Roeland: Thanks, Brittany. I think the questions also align with priorities for future research, and we need to recognize that the lack of evidence aligns with some of the challenges of funding research in this space. However, ongoing future research priorities include what is the nature of healthcare disparities pertaining to medical cannabis use by adults with cancer, and what are effective means to address these disparities? We also wonder, what are the optimal strategies to maximize communication in the oncology clinic regarding medical cannabis and/or cannabinoid use? And when we're thinking about cannabis and/or cannabinoids for cancer treatment specifically, we still need to know do cannabis and/or cannabinoids possess clinically meaningful anticancer activity in humans. We also need to understand what are the drug-drug interactions with our standard-of-care cancer treatments, including cytotoxic chemotherapy, targeted therapy, immunotherapy, radiation, and combinations of all the above. We also are wondering what the effect of cannabis and/or cannabinoids on outcomes in adults with cancer receiving some of our newer therapies, including antibody-drug conjugates and some of our newer vaccine therapies.  Dr. Ilana Braun: I might add that collating the existing research as the guideline did is a very good first step and should serve to highlight where the gaps in knowledge lie. This guideline discusses some of the unique challenges to conducting cannabis and cannabinoid research, including limitations in funding source and study drug, red tape procedures, and issues around legalization. I believe it will take a group of highly determined and creative researchers to move the needle forward in this area, but we must. Brittany Harvey: Definitely. Thank you both so much for all of your work developing this guideline and creating these evidence-based recommendations. And thank you for taking the time to come on the podcast today and teach us all a little bit more about cannabis and cannabinoids in cancer care. And thank you for your time, Dr. Braun and Dr. Roeland.   Dr. Ilana Braun: Thanks so much, Brittany. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Angela DeMichele, Dr. Lynn Henry, and Dr. Harold Burstein present the latest breast cancer rapid recommendation update impacting two ASCO guidelines. This update focuses on the new option, capivasertib plus fulvestrant, for patients with hormone receptor-positive, HER2-negative metastatic breast cancer with activating PIK3CA or AKT1 mutations or inactivating alterations in PTEN based on data from the recent CAPItello-291 trial. They discuss the updated recommendations on lines of endocrine treatment and selecting between the options for patients with activating PIK3CA mutations. Additionally, we discuss implications for clinicians and patients, and what ongoing research is occurring in the field. Read the latest update, “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer – Capivasertib-Fulvestrant: ASCO Rapid Guideline Update“ at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00248 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I am interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute, Dr. Angela DeMichele from the University of Pennsylvania, and Dr. Lynn Henry from the University of Michigan, co-chairs on “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Capivasertib–Fulvestrant: ASCO Rapid Guideline Update.” Thank you for being here, Dr. Burstein, Dr. DeMichele, and Dr. Henry. Dr. Harold Burstein: We're happy to be here.  Brittany Harvey: And before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests on this episode today, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to kick us off, Dr. Burstein, could you first describe what prompted this rapid update, which provides updated recommendations for two ASCO guidelines: the biomarkers for systemic therapy in metastatic breast cancer guideline, and the endocrine treatment and targeted therapy for hormone receptor-positive, HER2-negative metastatic breast cancer guideline? Dr. Harold Burstein: Thanks, Brittany. Well, this team has been working, as you mentioned, actually, on two guidelines, which are clearly evolving in parallel and kind of converging, actually, when you look at data, as we'll be talking about in the next few minutes. The particular catalyst here was a large randomized clinical trial which looked at a new targeted therapy in the space of estrogen receptor-positive, HER2-negative breast cancer. That drug is capivasertib. And the trial was the so-called CAPItello study. In that trial, patients who were receiving second-line therapy with fulvestrant were randomized to that treatment alone, or that plus capivasertib. So the data from that study were the first strong signal that we needed to update the guideline because they were important clinical data.   The other strong signal was that the drug was tested in a cohort of patients who had a specific set of mutations in their cancers. And that included PIK3CA mutations, a class of mutations for which we already had a targeted drug. But it also included some new potential targets, including mutations in the AKT gene itself, capivasertib is an AKT inhibitor, as well as loss of PTEN protein functionality, which potentially sensitizes tumors to the targeted action of this drug as well. So while we had a couple of guidelines catching up on the endocrine therapy space, which is increasingly looking like a targeted therapy space, it was clear that this major study, which had clinical and diagnostic implications, would sort of push them together and served as the impetus for updating both guidelines at the same time. Brittany Harvey: Understood. I appreciate that background information.   So then, Dr. DeMichele, based on this updated data that Dr. Burstein just described, what is the updated recommendation from the guideline panel regarding lines of endocrine treatment? Dr. Angela DeMichele: Well, I think this is where the biomarker evolution that Dr. Burstein just referred to really comes in because now we have the opportunity to perform genomic testing in patients who have ER-positive, HER2-negative metastatic breast cancer, on either the tumor or commonly from the blood. And we can now start to tailor treatment to the specific genomic abnormalities that that patient's tumor contains. So now our guideline really marries both the genomic abnormality with the therapeutic option. First-line treatment remains endocrine therapy plus a CDK 4/6 inhibitor. But things then really start to diverge once we enter second and third-line therapy because at that point, we now have the option to test for several genomic markers: ESR1 mutations, PIK3CA mutations, AKT1 mutations, and PTEN inactivation. And based on whether the tumor has one or any of those mutations, we can then select the therapy based on that.  So in the case of capivasertib, as you just heard, that is a therapy for patients whose tumors have PIK3CA mutations or activating mutations in AKT1 or loss of PTEN. But other patients who don't have one of those mutations may, in the second line, go on to another drug. For example, if they have an ESR1 mutation, they then may be eligible to take elacestrant. Patients who have no targetable mutations still have a targeted option in that they can use everolimus. And in all of these settings, the endocrine therapy partner for this line of therapy is typically fulvestrant. So now we're really starting to tailor therapy in the second- and third-line based on genomic changes. Brittany Harvey: Excellent. That information is helpful for choosing optimal therapy tailored to the individual patients, as you just described.  So then, Dr. Henry, what guidance does the expert panel provide regarding choosing a PIK3CA targeted option? Dr. Lynn Henry: Thank you. So for patients whose tumors are found to have an activating mutation in PIK3CA, we now have two drug options: either alpelisib or capivasertib in combination with fulvestrant. And the problem is, these drugs have not been compared head-to-head. We can't say that one is clearly better than the other, either in terms of efficacy or in terms of side effect profile. What we do have is information from two separate trials in which they were each tested against placebo. The efficacy appears to be fairly similar based on the data that we have. It does appear that the side effect profiles may be slightly different. And so, when you have a patient sitting in front of you and you're trying to decide how best to treat her, you really have to think about, what symptoms does my patient already have? What is she more or less likely to tolerate? So what we do know is that it appears that the rates of grade 3 diarrhea and rash were slightly higher with capivasertib. It looks like hyperglycemia was higher with alpelisib, as was treatment discontinuation. So really you have to make an individualized decision when you have a patient sitting in front of you about which drug you'd like to try. Of course, if someone doesn't tolerate one drug, you can always switch to the other one.  Brittany Harvey: I appreciate that analysis and to provide guidance without a head-to-head trial and to specifically provide options based on an individual patient's profile.   So then, Dr. DeMichele, what should clinicians know as they implement these new recommendations?  Dr. Angela DeMichele: Well, first of all, I think most clinicians now are becoming more familiar with the procedures required for doing genomic testing. But this is something that now has become the standard of care. And so, it is incumbent upon all of us who treat these patients to understand what the options for genomic testing are for that patient, which companies offer this testing, how to send a sample, and how to interpret the report that comes back. So, I think this has really added a level of complexity to the therapy for patients. I also think that one can’t simply apply an algorithm to a patient. We have to really treat the whole patient and we have to take into consideration, as Dr. Henry said, the toxicities of these agents and the cost which is also a major issue. So I think that while it is more complex, really that doctor-patient relationship is so important in communicating what these genomic tests mean for a patient and for their options, and also important for the clinician to really understand what the different therapeutic agents might mean for a patient, and really try to pick the agent that’s best for that patient. Using genomic testing is just one of several different features that they’ll consider. Brittany Harvey: Absolutely. It’s key to obtain the data needed to select appropriate patients and to recognize the complexity.   So then, Dr. Henry, in your view, how will this update impact patients with metastatic breast cancer? Dr. Lynn Henry: Yes, so as we’ve discussed, I think this is really exciting. Over the last few years, we have had quite a number of new medications that have become available for patients and have been FDA-approved. And so this is yet the latest in a series. For those patients whose tumors have a PIK3CA mutation, as we discussed, there are now two options. So you have a choice depending on which one is better covered by insurance, by which one you may tolerate better. But I think the other thing is now, although it’s a smaller subset of patients, there are patients out there whose tumors have mutations in AKT1 or alterations in PTEN, and so there’s an entirely new endocrine therapy-based option available for them that wasn’t available before. So I think that thinking about the new data that are out there, the new drugs that are out there, really is exciting because there are new options available and hopefully there are more to come as well.    Brittany Harvey: Absolutely. It's great to have these new options.  So, finally, Dr. Burstein, Dr. Henry just mentioned what's to come. Could you touch on what some of the outstanding questions are regarding endocrine therapy for patients with metastatic breast cancer?  Dr. Harold Burstein: A couple of things to say. First, ER-positive metastatic breast cancer is the most common kind of metastatic breast cancer, roughly three quarters of metastatic cases of breast cancer will be hormone receptor-positive cancers. So this is a very big public health issue around the world, actually, breast cancer being the number one most commonly diagnosed cancer of women around the world. So minor or major improvements in treatment for advanced ER-positive breast cancer really have a tremendous impact.  The second thing is it’s been remarkable to see the progress in the past decade. We’ve gone from simply targeting the hormonal access itself with medicines like tamoxifen or aromatase inhibitors or an injectable selective estrogen receptor degrader like fulvestrant to incorporating targeted therapies at the same time. And this whole class of drugs called CDK4/6 inhibitors has emerged which we use in either first- or in second-line therapy. Those drugs have transformed our standard of care, improved survival for patients with advanced ER-positive disease, now with median survival nearly 50% longer than what we had seen in the past.  And if you’ve heard, we have a wealth of opportunities. We can target PIK3CA, we can target ESR1 mutations. Other drugs emerging in the space include PROTACs which is another way of degrading the estrogen receptor. And so there’s going to be more progress in the years to come.   So one of the biggest challenges has been to try and understand, is there really an optimal way to use these drugs, or can we be smarter about the particular sequence of all these particular things that are happening.  So one example of this was a recent study that is on a drug, not as yet FDA-approved, called inavolisib, which is a PIK3CA targeted drug used in first line in combination with a CDK4/6 inhibitor and endocrine therapy. And that study, for a high-risk group of women with ER-positive metastatic disease, actually showed a dramatic improvement in overall survival, asking the question if combining some of these targeted therapies together might yet further improve outcomes.  And as you’ve heard from the diagnostic space, one of the other interesting things is that tumors evolve over time. And so acquisition of the estrogen receptor mutations, ESR1 mutations, which are typically not found early in the course of advanced breast cancer but otherwise later, now have targeted treatments. So there’s a whole bunch of stuff going on all at the same time, including multiple ways of targeting things, serial testing to look for acquisition of ESR1 mutations and new pathways to explore. It’s an embarrassment of riches in some respects because it has meant it’s actually really hard to write a guideline as you’ve heard, which says, “Do this first, do this second, and do this third.” I suppose that’s a good problem to have under the circumstances, but it’s going to require really thoughtful clinical trials and careful analysis to help guide specific lines of treatment recommendations like that.  Brittany Harvey: Excellent. We’ll look forward to these exciting, continuing developments for patients with metastatic breast cancer. And I want to thank you all so much for your work to develop this rapid recommendation update for these two guidelines. And thank you for taking the time on this podcast today. Dr. Harold Burstein: Thanks. Dr. Lynn Henry: Thank you so much.  Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.