An interview with Dr. Mark Kris from Memorial Sloan Kettering Cancer Center in New York, NY, author on "Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA Completely Resected NSCLC: ASCO Guideline Rapid Recommendation Update." Dr. Kris discusses the results and impact of two recently published RCTs, and the updated recommendations on the use of osimertinib and atezolizumab. For more information, visit, www.asco.org/thoracic-cancer-guidelines.

TRANSCRIPT

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BRITTANY HARVEY: Hello and welcome to ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts.

My name is Brittany Harvey, and today I'm interviewing Dr. Mark Kris, from Memorial Sloan Kettering Cancer Center in New York, New York, author on Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage One to 3A Completely Resected Non-small Cell Lung Cancer ASCO guideline rapid recommendation update. Thank you for being here, Dr. Kris.

MARK KRIS: You're very welcome. And on behalf of the Adjuvant Guideline Committee, thank you for giving this opportunity today to speak to you. I have had financial report from AstraZeneca, Pfizer, Sanofi Genzyme, and also editorial support from Hoffman-La Roche.

Every year, 35,000 Americans received the diagnosis for early stage lung cancers. And that is, lung cancers that could be helped by surgery. It's a large number of patients. Many of them can be cured by operations, but not all. When people fail to be cured by surgery, the problem is not an unsuccessful surgery, but rather the spread of cancer to other parts of the body, very often cancer that's not suspected by any test that we have in 2022.

What physicians do is to give medicines before or after surgery to try to increase the chance of cure with a successful surgery. And the guideline we're talking about today deals with the recommendations of the American Society of Clinical Oncology Adjuvant Lung Cancer Guideline Committee for new treatments to increase the chance of cure in patients that have successful lung cancer surgeries.

BRITTANY HARVEY: Great. Thank you, Dr. Kris, for both that background and for providing your disclosures for this guideline. You just mentioned what this guideline's purpose is, but this is specifically a rapid update. So what prompted this rapid update to the adjuvant systemic therapy and adjuvant radiation therapy for stage one to 3A completely resected non-small cell lung cancers, which was last updated in 2017?

MARK KRIS: In the last year, there have been extremely important developments in the lung cancer field. There have been two medicines that have been proven to delay or prevent the recurrence of lung cancer after a successful surgery. One of them is a targeted therapy, the other an immunotherapeutic. And both of these medicines have had the clinical trials that discovered them presented at major meetings, including the ASCO meeting.

They also have had major publications in medical journals. And both of these medicines are now FDA approved. This is a new therapy, great addition to our therapy, and it includes drugs that are available to every doctor in the United States for patients in this situation. So there was the need to get this information out early and to get the word out to doctors everywhere to consider these medicines for the appropriate patients.

BRITTANY HARVEY: Understood. Then based off this new data for these new therapies that you just mentioned, what are the updated recommendations from the guideline panel?

MARK KRIS: The current recommendations, and I'll break it up into two settings. One of them is for stage 1B, B as in boy. And these are larger tumors, but only tumors in the lung. And the second set of recommendations are for lung cancers that also have evidence of spread to the adjacent lymph nodes or lymph glands.

Now up until these new recommendations, for the people with the 1B cancer, and that is the larger tumor only in the lung, the recommendation was there was no routine recommendation. That each case got discussed individually and a decision was made whether or not to recommend a chemotherapy program based on the drug cisplatin. It's not right for every patient and requires a fair amount of discussion and evaluation to decide who it's right for.

What the guideline adds now, though, is for genetic testing of the tumor tissue removed at surgery to search for the presence of a certain mutation, the EGFR mutation, in the tumor tissue. And if that mutation is found, the recommendation is to give the drug osimertinib, a pill, for three years following a successful surgery and following chemotherapy. What they found in that trial was that people who received this pill had a clear and dramatic improvement in the return of the cancer.

The cancer was greatly delayed or, hopefully as time goes on, we'll learn did not return at all. This is an important change, because up until then, there was no specific recommendation for patients in this 1B group. Now if you have the EGFR mutation in the tumor, we are recommending that every patient could receive osimertinib.

The other big change here is because there is the need to know if a mutation is present, part and parcel of that is the routine testing of tumor tissue. To make this happen, your surgeon and medical oncologist need to obtain tumor testing on every person to see if these EGFR mutations are present. And if indeed they are, to recommend osimertinib.

The second development was the identification of a drug called atezolizumab. And this is a drug that energizes the immune system. They call it a checkpoint inhibitor, an anti-PD-1 PD-L1 drug, a lot of different names. What they found in this second trial is that patients whose tumor tissue had some identified presence of this particular protein, the PD-L1 protein, again, a routine test, if you had this protein present and you received the atezolizumab, you, again, had improvement in the delay of cancer and as time goes on, hopefully that the cancer won't return at all.

Again in that trial, the use of the atezolizumab followed cisplatin-based chemotherapy, our old recommendation. So these two papers led to these really important changes in our recommendations to all patients with this illness. Patients with EGFR mutations get osimertinib. Patients that don't have an EGFR mutation but instead have expression of pd-l1 and have a lung cancer that's in a lymph gland as well as the lung, they routinely now have the checkpoint inhibitor, atezolizumab recommended.

BRITTANY HARVEY: Thank you for that summary of these new recommendations. So then what should clinicians know as they implement these recommendations for osimertinib and atezolizumab?

MARK KRIS: One change in treatment that these new medicines have brought about is the need to do genetic testing, generally a comprehensive panel of genetic testing, some call it NGS testing, multiplex testing, on the tumor tissue removed at surgery. You need to know if this EGFR mutation is present. And if so, you're a candidate to receive the osimertinib stages 1B, stage two, and stage 3A.

Conversely, if that EGFR mutation is present, the benefit from atezolizumab is much less. And for those patients, to know if atezolizumab could be useful, you need to do a separate test, a so-called immunohistochemistry test. That can be done in any pathology department in the US. And this test looks for the presence of this pd-l1 protein. And if the protein is there, it means that the drug atezolizumab can be useful. And that mutation is found really in the majority of patients that don't have the EGFR mutation.

BRITTANY HARVEY: Great. And then in your view, how will these guideline recommendations impact patients?

MARK KRIS: Well, we are very interested in delivering to our patients what they want. And that is, after surgery to live lives free of cancer and to live lives as they choose and a life not dictated by the cancer. The way to do that is to prevent the recurrence of the cancer, extend the time that they are free of cancer so they can live their normal life. And both of these medicines have been able to do that. What we can do now is offer patients the chance for a more normal life, or extension of their normal life without cancer by adding on these new medicines after cisplatin-based chemotherapy and after their surgery.

BRITTANY HARVEY: Definitely. This is an important intervention for patients. So then finally, Dr. Kris, what are the outstanding questions regarding adjuvant therapy for patients with stage one to 3A completely resected non-small cell lung cancer?

MARK KRIS: I think the biggest question that remains is what do we do for those patients that don't have the EGFR and don't have this pd-l1 standing? At present, our recommendation is that we would recommend cisplatin-based chemotherapy. And there would be some consideration for radiation as well if there's a spread to mediastinal lymph glands, and I would urge a consultation with the radiation oncologist when the mediastinal lymph glands were involved with the cancer to see if that can be helpful. But we don't have this extra treatment today to recommend to these patients like we do for the ones with EGFR and pd-l1.

The second thing we'd like to do would be able to better tell who needs these extra treatments and who needs more intensive extra treatments. Some people are cured by surgery alone. And it would be fantastic to know who those people were so as to focus our efforts on those people that need additional therapy and spare the people that don't need additional therapy the lifestyle disruption that comes on with treatment. And there are a bunch of emerging technologies, and I want folks to know that docs across the country, researchers, are working hard to find ways to say, who needs the treatments.

And three things are being tested now. One of them is a more detailed examination of the tumor tissues. This is particularly important in patients that got their chemotherapy before surgery, and our pathology colleagues are working to see how effective treatments are given the drugs before surgery. And there's more and more a push to give drugs not after surgery, but before surgery, because then we can tell in the tumor specimen that's removed at the time of surgery if they worked or not.

The second thing is to examine these tissues, not just with the eye of the pathologist under the microscope, but to use digital images and to use artificial intelligence to look at the tumors that are present, and perhaps also tumor that's present after initial therapy, and take the appearance of that cancer and correlated with the long term outcome. So to be able to tell using machine learning, artificial intelligence, advanced computing systems, whether or not the cancer is likely to recur.

And there's been some preliminary work in this presented at the ASCO meeting last year that this promise appears to be inching toward reality. It's not simply pi in the sky. The last thing that's being developed is the ability to look for traces of cancerous DNA in the bloodstream. What you would do is check for cancerous DNA before surgery and check again after surgery.

And if we find that cancerous DNA persists in the bloodstream, that would be a trigger to give therapy or give more intensive therapy. And a number of clinical trials have already reported on this that it is feasible and possible, and the early results are that it likely will be another way to tell who will benefit from therapy, who needs it most, and hopefully who doesn't need it, if we can. So a lot of questions to be answered, a huge amount of research. I'm quite confident that it's going to lead to more effective therapies. It's going to lead to more targeted therapies and it's going to lead to sparing patients from getting treatments when their cancer is already taken care of.

BRITTANY HARVEY: Absolutely. We look forward to that promising research to improve outcomes for patients. So I really want to thank you for all your work on this guideline rapid recommendation update and for taking the time to speak with me today, Dr. Kris.

MARK KRIS: And if I could just say a final word, I'm doing this today on behalf of the Guideline Committee led by Laurie Gaspar from University of Colorado in Denver and Katherine Pisters from M.D. Anderson. They and the other panel members very quickly did this. This whole process happened in just a few months. It was very quickly brought together and posted on the ASCO website. I believe it was posted on January 10th and will shortly appear in the Journal of Clinical Oncology to get the word out.

I think to me it's a testimony to ASCO's willingness to quickly get out cancer advances to our patients and the process that ASCO has put in place, I think, worked really well here, going from an idea to get this information out to getting it out to practitioners all over the country in just a few months.

BRITTANY HARVEY: Absolutely. We thank the co-chairs and the entire panel for their work on this guideline. And also, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/thoracic cancer guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes 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.

SPEAKER 1: 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.

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