ASCO Education

Dr. Shaheenah Dawood is the Head of Medical Oncology and the Head of the Breast Cancer Program at Dubai Hospital in the United Arab Emirates. Dr. Dawood completed her M.B.B.Ch at Dubai Medical College in 1998 and a Master of Public Health degree at the Harvard School of Public Health, Boston, USA in 2008. Her postgraduate medical training programs include a Fellowship at McGill University in Canada in 2006, and the Susan Komen Breast Cancer Fellowship at the University of Texas M.D. Anderson Cancer Center in 2007. Dr. Dawood is a member of various professional organizations, including the American Society of Clinical Oncology (ASCO), the American Association of Cancer Research (AACR), the Canadian Association of Medical Oncologists, the Emirates Medical Association, and the Inflammatory Breast Cancer Research Group. She is also the co-director of the Middle East Research Network. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT [MUSIC PLAYING] Welcome to the self-evaluation episode of the ASCO University Weekly Podcast. My name is Shaheena Dawood, and I am a consulting medical oncologist and lead of the Oncology Research program at the Comprehensive Cancer Center at the Mediclinic City Hospital in Dubai, United Arab Emirates. Today, we feature a self-evaluation question looking at the predictive and prognostic role of pathological complete response attained in the treatment of breast cancer. Let us begin by reading the question stem. Here, we have a 55-year-old woman who presents with a 4 centimeter right breast mass and palpable right axillary lymph nodes. A needle biopsy of the breast mass and a lymph node are both positive for infiltrating ductal carcinoma negative for hormone receptors and negative for HER2/neu expression. The patient is interested in breast-conserving therapy, and she is referred to you for consideration of neoadjuvant chemotherapy. Which of the following do you tell her? Your choices are, A-- patients having a complete response to neoadjuvant chemotherapy have lower local and regional recurrence rates, B-- mastectomy will be required regardless of clinical response to chemotherapy, C-- chemotherapy will be administered before and after surgery, or D-- randomized trials have shown that radiotherapy is not necessary following surgery and chemotherapy if she has a complete response. At this point, please feel free to pause the recording before we discuss the correct answer. [MUSIC PLAYING] The correct answer to this question is A. Pathological complete response in the breast and lymph nodes is associated with lower local and regional recurrence rates. A combined analysis of the NSABP B18 and B27, two large trials that evaluated the role of neoadjuvant chemotherapy, revealed that the rate of local regional recurrence decreased amongst patients who initially presented with positive lymph nodes prior to neoadjuvant chemotherapy, and who become pathologically node negative after neoadjuvant chemotherapy, especially if they also achieved a pathological complete response in the breast. Briefly, the other choices presented in this question do not represent the most appropriate answer for the following reasons. The decision regarding type of surgery in the form of mastectomy versus breast-conserving surgery is dependent on multiple factors. One of the early established benefits of neoadjuvant therapy is that it increases the probability of breast-conserving surgery, making more women candidates for lumpectomy and breast radiotherapy, who otherwise would have been treated with mastectomy. Studies have shown that chemotherapy before surgery in the neoadjuvant setting versus chemotherapy after surgery in the adjuvant setting is associated with similar outcomes. And finally, attaining a pathological complete response currently does not preclude the need for adjuvant radiation therapy, the decision of which would be made on clinical stage of disease at presentation. The NSABP51 RTOG phase III trial is ongoing to evaluate the role of regional radiotherapy in women presenting with clinical N1 axillary node disease before neoadjuvant chemotherapy, and who become pathologically node negative at the time of surgery. Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the treatment of breast cancer, including opportunities for self-evaluation and board review, please visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING] 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

This week's host, Dr. Thomas Karasic, is an assistant professor at University of Pennsylvania specializing in the treatment of gastrointestinal malignancies. In this episode, Dr. Karasic discusses the recent FDA approval of lenvantinib for patients with unresectable hepatocellular carcinoma. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT [MUSIC PLAYING] Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Thomas Karasic, I'm an assistant professor at the University of Pennsylvania, specializing in the treatment of gastrointestinal malignancies. Today, we will discuss the approval of lenvatinib for the treatment of patients with un-resectable hepatocellular carcinoma. As background to our discussion today, the only FDA approved therapy prior to 2017 for hepatocellular carcinoma was sorafenib. This is based on results of the SHARP trial published in the New England Journal in 2008, which demonstrated an overall survival benefit of 10.7 months in the sorafenib arm, versus 7.9 months in the placebo arm. In the 10 years after the approval of sorafenib, a number of phase III trials attempted to establish additional drugs or combination regiments in both the first line and the second line setting for advanced hepatocellular carcinoma. But all trials failed to meet their primary endpoint, and no other treatments were approved. However, in 2017, two new drugs were approved for the second line treatment of hepatocellular carcinoma-- regorafenib, a drug similar to sorafenib, as well as the PD-1 inhibitor, nivolumab. Lenvatinib is an anti-angiogenic tyrosine kinase inhibitor that targets VEGF-1 3, FGFR 1 through 4, PDGFRA, KIT, and RET. On August 16, 2018, lenvatinib was FDA approved for the first line treatment of un-resectable hepatocellular carcinoma. Two different doses were approved-- 12 milligrams for patients with actual body weight greater than or equal to 60 kilograms, and 8 milligrams for patients with actual body weight less than 60 kilograms. The approval of lenvatinib in the first line setting was based on the results of a non-inferiority study comparing lenvatinib to sorafenib for unresectable hepatocellular carcinoma. The primary endpoint of the study was overall survival. A total of 1,492 patients were recruited, and 954 patients were randomized one-to-one between lenvatinib or sorafenib. Lenvatinib was given at a dose of 12 milligrams daily for patients of at least 60 kilograms actual body weight, or 8 milligrams for those below 60 kilograms-- while sorafenib was given at the FDA approved dose of 400 milligrams twice daily. This trial met its primary endpoint of non-inferiority for overall survival. Overall survival was 13.6 months in the lenvatinib arm, and 12.3 months in the sorafenib arm. While it met its endpoint for non-inferiority, it did not establish superiority in terms of overall survival. The hazard ratio for overall survival was 0.92. Lenvatinib did demonstrate a statistically significant increase in time to progression-- 8.9 months in the lenvatinib arm, versus 3.7 months in the sorafenib arm. It also showed a statistically significant improvement in overall response rate. Using the study endpoint of modified RECIST criteria, the objective response rate with lenvatinib was 41% versus 12% with sorafenib. Using more standard RECIST 1.1 criteria, the overall response rate of lenvatinib was 19%, versus 7% with sorafenib. Adverse events were common in both arms of the study, with 57% of those treated with lenvatinib experiencing grade 3 or greater toxicity, compared to 49% of those treated with sorafenib. Toxicities that were more common with lenvatinib included hypertension, proteinuria, hypothyroidism, weight loss, anorexia, nausea, and vomiting-- while sorafenib more commonly had hand/foot syndrome and alopecia. Toxicities, such as fatigue and diarrhea, were similar between the two arms. The approval of lenvatinib marks the first positive front line study comparing an agent to sorafenib in the first line treatment for HCC. Lenvatinib demonstrated improvements in overall response rate, as well as progression-free survival, and a modest trend towards improved overall survival, although this was not statistically significant. The toxicities of sorafenib and lenvatinib were largely comparable, although some toxicities-- such as hand/foot syndrome are more common with sorafenib-- whereas hypertension and proteinuria are more common with lenvatinib. These study results established lenvatinib as a reasonable firstline option for the treatment of HCC, and choice of sorafenib versus lenvatinib can be made based on toxicity profile, as well as the symptoms of the patient that may dictate the need for an agent with a higher response. Pending results from the CheckMate 459 study, as well as other ongoing immunotherapy front line studies, may well change the sequence of immunotherapy and anti-angiogenic therapy for HCC. But for now, lenvatinib is a reasonable front line option. Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on lenvatinib and the treatment of hepatocellular carcinoma, visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING] 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT Welcome to the Self-Evaluation episode of the ASCO University weekly podcast. My name is Dr. Karen Winkfield, and I am Associate Director for Cancer Health Equity and Director of Hematologic Radiation Oncology at the Comprehensive Cancer Center at Wake Forest Baptist Health in Winston-Salem North Carolina. Today, we feature a self-evaluation question on the treatment of multiple myeloma and other plasma cell dyscrasias, and we begin by reading the question stem. A 65-year-old woman was found to have free light-chains in her urine after she presented with proteinuria. A 24-hour urine collection contained 0.6 grams of monoclonal lambda light-chains, and the urinary sediment was normal. She had normal complete blood count, renal function, and serum lactate dehydrogenase and calcium levels. Serum protein electrophoresis was normal with no monoclonal component. Subsequent free light-chain, or FLC, studies revealed kappa at 68.5 milligram per liter and lambda at 16.7 milligram per liter with FLC ratio of 4.1 with a normal range of 0.26 to 1.65. The bone marrow aspirate revealed 6% of mature-looking plasma cells. Bone marrow biopsies failed to demonstrate any amyloid deposits. Both conventional and fluorescent in situ hybridization cytogenetic analyses were normal. Skeletal X-rays, as well as spinal access MRIs were normal. The diagnosis is light-chain monoclonal gammopathy of undetermined significance, or LC MGUS. Which of the following is an accurate description of this disease? A, around 30% of cases present with kidney disease. B, around 3/10 of 1% per year of cases progress to light-chain multiple myeloma. C, around 30% of all MGUS is comprised of this condition. D, around 3% of the general population older than 50 years has this condition. [MUSIC PLAYING] The correct answer to this question is B, around 3/10 of 1% per year of cases progress to light-chain multiple myeloma. This answer reflects the natural history of LC MGUS. Briefly, the other choices presented in this question are incorrect for the following reasons. Approximately 23% of LC MGUS cases have or will develop renal disease. Therefore, answer A slightly overstates the incidence at 30%. Similarly, LC MGUS comprises only 19% of total cases of MGUS. This is consistent with the proportion of light-chain multiple myeloma cases among newly-diagnosed multiple myeloma patients. An estimated 0.8% of the general population age 50 years and older has LC MGUS. Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on the treatment of multiple myeloma and other plasma cell dyscrasias, visit the comprehensive E-Learning Center at university.asco.org. [MUSIC PLAYING] 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.

TRANSCRIPT [MUSIC PLAYING] Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan-Kettering Cancer Center, and editorial board member for ASCO University. Today, we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines podcast series. My name is Shana McKernan, and today, I'm interviewing Dr. Antonio Wolff from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, an author on HER2 Testing in Breast Cancer, American Society of Clinical Oncology College of American Pathologists Clinical Practice Guideline Focus Update. Thank you for being here, Dr. Wolff. Thank you for the opportunity. It is really a privilege to be here today on behalf of all of my colleagues in the ASCO/CAP HER2 testing panel, which truly represents not just a multi-disciplinary, but a multi-society effort over many years. First, can you give us a general overview of what this guideline covers? The recommendations by the ASCO/CAP HER2 testing expert panel were first released in 2007 and updated in 2013. And this is now a 2018 focus update. The aim was to improve the analytic validity of HER2 testing and the utility of HER2 as a predictive biomarker for potential responsiveness to therapies targeting the HER2 protein. In fact, in late 2017 at the San Antonio Breast Cancer Symposium, we finally had data from the NRG trial B-47, which confirmed the lack of benefit from adjuvant trastuzumab for patients whose tumors lack gene amplification and were IHC 1+ or 2+. As a result, HER2 gene amplification assessed by In Situ Hybridization-- ISH, or I-S-H, or protein overexpression assessed by immunohistochemistry, IHC, remained the primary predictors of responsiveness to HER2-targeted therapy in breast cancer. We have seen over the years a great communication among health care providers, especially pathologists and oncologists, but also much-needed infrastructure support by administrative teams regarding specimen handling in lab facilities. And they have resulted in meaningful improvements in the analytic performance and accuracy of HER2 testing. We also have had greater clinical experience with the efficacy and safety of HER2-targeted therapies that resulted in a meaningful reduction in the high frequency of false-positive HER2 test results that were observed in the mid 2000s. And this led to the 2013 guideline update panel to provide further guidance regarding less-common clinical scenarios to allow greater discrimination between positive and negative results. Since 2013, since the 2013 update, several labs and clinical investigators have reported on the practical implications of the guideline update and the observed frequency of equivocal cases. And these results have allowed the panel recently to evaluate the observed frequency of less-common HER2 testing patterns, the apparent prognostic and predictive value when retrospectively analyzed within clinical trial data sets, and the critical need to understand the underlying distribution of HER2 immunohistochemistry test results in cases that were submitted for additional tests, specifically In Situ Hybridization by a reference lab. This all led to the ASCO/CAP HER2 testing panel to prepare and now issue this 2018 HER2 testing focus update that includes five key recommendations. What are the key recommendations of this guideline? The HER2 testing guideline panel identified five clinical questions that formed the core of the 2018 focus update. Clinical question one is, what is the most appropriate definition of IHC 2+ or IHC equivocal. And clinical question two asks whether HER2 testing must be repeated on a surgical specimen if initially negative tests on a core biopsy. And these two questions were addressed in a previous correspondence by the panel that was published in the JCO in 2015. And they referred specifically to Figure 1, the algorithm for immunohistochemistry testing, and Table 2, the histopathologic features suggestive of possible test discordance. Clinical questions three, four, and five address less-common patterns observed when performing dual-probe In Situ Hybridization testing, and are now graphically summarized in four different figures, Figures 3 to 6, that focus on the algorithm for dual-probe In Situ Hybridization testing. And these three questions help clarify the 2013 recommendations that led some labs to adopt the use of multiple alternative chromosome 17 probe testing as the sole strategy to resolve equivocal HER2 test results by In Situ Hybridization, despite limited evidence on analytical and clinical validity of such strategy. The three additional questions of the 2018 focus updates are clinical question three, should invasive cancers with HER2/CEP17 ratio of 2.0 or higher, but an average HER2 copy number of less than 4 signals per cell, be considered ISH-positive. Clinical question four, should the invasive cancers with an average HER2 copy number of 6.0 or greater signals per cell, but a HER2/CEP17 ratio of less than 2.0 be considered ISH-positive? And finally, clinical question five, what is the appropriate diagnostic workup for invasive cancers with an average HER2 copy number 4.0 or higher, but less than 6.0 signals per cell, and a HER2/CEP17 ratio less than 2.0, and initially found to have an equivocal HER2 ISH test result. The recommendations regarding dual-probe ISH testing also led to a change in figure 2 that describes the algorithm for single-probe ISH testing, and includes a new footnote with a recommendation that concomitant immunohistochemistry review should become part of the interpretation of single-probe In Situ Hybridization results. The 2018 HER2 testing focus update also includes a new Table 3 that describes the patterns of HER2 ISH testing using dual probe assays showing a clear impact of the underlying distribution of HER2 immunohistochemistry test results on the frequency of these less common patterns of In Situ Hybridization. As we expect, in total, groups 2, 3, and 4 will represent no more than 5% of all cases tested by In Situ Hybridization. And the majority, 95% of cases, tested for HER2 by dual-probe In Situ Hybridization will consist of group 1, which are clearly HER2-positive , and group 5, HER2-negative. And ultimately, the available clinical outcome data from related trials, although of limited statistical power, have allowed the panel to more carefully define this expected prognostic and predictive behavior of cases tested by dual-probe In Situ Hybridization that will fall in groups 2, 3, or 4. What are the major changes from the 2013 version of this guideline? Most important, after consideration of the available evidence and expert opinions, the ASCO/CAP HER2 testing panel revised the diagnostic approach to groups 2, 3, and 4 to include more rigorous interpretation criteria for dual-probe In Situ Hybridization testing, and to require concomitant immunohistochemistry review to arrive at the most accurate HER2 status designation, positive or negative, based on the combined interpretation of the ISH and the IHC assays. The panel therefore recommends that such concomitant review be performed in the same institution to ensure parallel interpretation and quality of the two assays. As a result, most group 2 specimens will not be confirmed as HER2-positive, as very few will be immunohistochemistry 3+, and most group 4 specimens will be confirmed HER2-negative without the need for additional testing, use alternative probes, which happen a lot since 2013. At the same time, group 3 specimens will be a mixed group of results with a small number of cases shown to be amplified, and a larger number shown not to be amplified. And so for these dual-probe ISH group 3 cases, the panel allows specimens that are IHC 2+ to be considered HER2-positive. And the rationale is described in greater detail in the manuscript. And finally, how will these guideline recommendations affect patients? While the main focus was to clarify the less common test results observed with the two-probe ISH assays, the recommendations do impact users of single-probe ISH assays. As such, the panel now recommends that concomitant immunohistochemistry review should become part of the interpretation of single-probe In Situ Hybridization results to allow a more accurate HER2 designation. And this is nicely described in Figure 2. And the panel also preferentially recommends the use of dual-probe instead of single-probe ISH assays, while it recognizes that several single-probe ISH assays have regulatory approval in many parts of the world. At the end, and to conclude, these actions, we hope, will reduce the already small number of cases that have HER2 test results that are unresolved, will reduce the frequency of alternative group testing, and will remind us all of the importance of integrating the information provided by both types of assay platforms, IHC and ISH, in difficult cases, as we expect these results to be concordant in the vast majority of cases, when expertly performed. Thank you for your insights on this guideline, and thank you for your time today, Dr. Wolff. Thank you so much. And thank you to all of our listeners for tuning in to the ASCO guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. [MUSIC PLAYING] 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

TRANSCRIPT Welcome to the Self-Evaluation episode of the ASCO University weekly podcast. My name is Apar Kishor Ganti, and I'm the Associate Director for Clinical Research and the co-leader of the Thoracic Oncology Service at the University of Nebraska Medical Center, Fred and Pamela Buffett Cancer Center. Today, we feature a self-evaluation question on locally advanced non-small cell lung cancer. I will begin by reading the question stem. A 58-year-old man with a 50-pack year history of smoking presents to your clinic with worsening cough and shortness of breath. His comorbidities include irritable bowel syndrome and coronary artery disease. A CT scan of the chest, abdomen, and pelvis reveal a two-centimeter right lower lobe mass with no evidence of lymphadenopathy in the chest. A positron emission tomography scan confirms a hypermetabolic right lower lobe mass and mildly avid mediastinal nodes. An MRI of the brain was performed and was negative. A biopsy of the right lower lobe mass was positive for squamous cell carcinoma of the lung. The patient was taken for a mediastinal lymph node evaluation by a thoracic surgeon. Additional biopsies of multiple lymph nodes were taken. Pulmonary function tests revealed that a right lower lobectomy would be feasible if warranted. Which of the following would lead you to recommend definitive chemoradiation rather than surgery as the most appropriate treatment for this patient? The answer choices are, A, metastatic squamous cell carcinoma identified in a left hilar lymph node, B, metastatic squamous cell carcinoma identified in a right hilar lymph node, C, the absence of squamous cell carcinoma in a left paratracheal lymph node, and D, the absence of squamous cell carcinoma in a right hilar lymph node? [MUSIC PLAYING] The correct answer to this question is A, metastatic squamous cell carcinoma identified in a left hilar lymph node. In the eighth edition of the AJCC TNM classification system, this tumor would be classified as T1B. The presence of cancer in a contralateral hilar lymph node represents N3 disease and thus, stage 3B. Surgery is not recommended in this setting, and definitive chemoradiation is considered standard of care. What about the other choices? Involvement of an ipsilateral hilar node would only represent N1 and stage 2B disease, for which a right lower lobectomy and mediastinal lymph node dissection are appropriate. The absence of involvement of the left paratracheal node would confirm the absence of N3 disease, while the absence of involvement of the right hilar node would confirm the absence of N1 disease. In both these scenarios, the patient would be considered resectable if other lymph node stations are not involved. Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on lung cancers, including important release for self-evaluation, visit the comprehensive E-Learning Center at university.asco.org. Thank you. [MUSIC PLAYING] 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

TRANSCRIPT [MUSIC PLAYING] Welcome to the ASCO Guidelines episode of the ASCO University weekly podcast. My name is Alexander Drilon, and I'm the clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and editorial board member for ASCO University. Today we feature an ASCO guideline published in the Journal of Clinical Oncology. The episode you are about to hear was originally aired on the ASCO Guidelines podcast series. The ASCO Guidelines podcast series features interviews with panelists of recently published ASCO clinical practice guidelines products, highlighting recommendations and noteworthy qualifying statements made by the expert panel. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Davendra Sohal from Cleveland Clinic, lead author on Metastatic Pancreatic Cancer American Society of Clinical Oncology Clinical Practice Guideline update. Thank you for being here today, Dr. Sohal. Thanks for having me. It's a pleasure. So this update is focused on revising the recommendations on second line treatment for metastatic pancreatic cancer. Can you tell us about the studies that informed this update? Certainly. The first study is a paper published in Science on PD-1 inhibition and solid tumors. This study included 86 patients with mismatch repair deficient tumors, also known as microsatellite instability high tumors. In this study, 53% of the patients had an objective response with a disease control rate of 71% across multiple histologies. The study also included eight patients with pancreatic cancer, two of whom had complete responses with a disease control rate of 75%. This is the study that informed our recommendation for checkpoint inhibitor therapy in the second line setting. The second study is the PANCREOX trial published in JCO, which randomized patients to 5-fluorouracil or FOLFOX. With 108 patients, the primary outcome of overall survival was 9.9 months in the control 5-fluorouracil arm, and surprisingly, only 6.1 months in the FOLFOX arm. This study informed our recommendation for chemotherapy regimens in the second line setting. And what are the new and updated recommendations for second line treatment? For second line treatment of metastatic pancreatic cancer, our first recommendation now is to consider testing for mismatch repair deficiency or microsatellite instability in patients who are candidates for checkpoint inhibitors therapy. Any standard form of testing is acceptable, whether IHC or PCR or next-gen sequencing. Patients who have mismatch repair deficient or microsatellite instability high tumors should be treated with pembrolizumab given the excellent responses noted in the study we just discussed. For patients who do not meet these criteria for checkpoint inhibitor therapy, second line therapy with gemcitabine plus nab-paclitaxel can be offered to those who received FOLFIRINOX in the first line and meet other criteria for aggressive chemotherapy as detailed in the guideline. Now, for patients who receive gemcitabine plus nab-paclitaxel in the first line, fluorouracil plus nanoliposomal irinotecan is the preferred second line therapy. Where nanoliposomal irinotecan is not accessible, fluorouracil plus regular irinotecan is an acceptable alternative. As I mentioned the combination, of 5-fluorouracil plus oxaliplatin can be considered as an option in this setting, but we have noted a qualifying statement about the PANCREOX study whose results are inconsistent with the CONCORD-3 study using the same agents as the off regimen. Given these conflicting results from different studies of 5-fluorouracil plus oxaliplatin, the recommendation for its use in the second line setting has been softened. Can you also give us an overview of the recommendations from the original 2016 version that the expert panel decided were still valid? Sure. In 2016, the expert panel made recommendations which span from initial assessment through to follow up and surveillance. For every patient with metastatic pancreatic cancer, a multi-phase CT scan should be performed and baseline performance datas and comorbidities should be evaluated. Goals of care should be discussed with a multidisciplinary team, and all patients should be offered information about clinical trials. Outside of a clinical trial, standard first line treatment options include FOLFIRINOX, gemcitabine plus nab-paclitaxel, or gemcitabine alone. And the full guideline provides details on which treatment is appropriate for which patients. The panel also recommended that every patient should be offered palliative care early in their treatment. These recommendations were endorsed in the update and are reprinted in totality in the bottom line box on the second page of the article. And finally, what are some important things to note about communicating with patients with pancreatic cancer, especially in the metastatic setting? Excellent point. It is important to communicate that participation in clinical studies is strongly encouraged. These studies could include new treatments, or supportive care measures, or collection of blood and tumor samples for further research, et cetera. While chemotherapy forms the backbone of treatment, it is only one component, and that is an important point to make. The use of supportive care or palliative care is strongly encouraged for all patients with metastatic pancreatic cancer in order to maximize not just the quantity, but also the quality of life. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Sohal. Sure. Thank you very much. I'd like to thank our panel for diligent data review and dedicated discussions and the ASCO staff for all their support in producing the update. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague. [MUSIC PLAYING] 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

2018 Annual Meeting raised the curtain on a new session type: ASCO Voices. These noncompete session feature presentations no longer than 7 minutes each and bring a variety of perspectives to the stage to share stories on oncology, medicine, and the world. From big ideas to personal passions, ASCO Voices present stories that differ significantly from the remainder of session types available at Annual Meeting.

[MUSIC PLAYING] Welcome to the self-evaluation episode of the ASCO University Weekly Podcast. My name is Teviah Sachs, and I am an Assistant Professor of Surgery at the Boston University School of Medicine and Surgical Oncologist at Boston Medical Center. Today we will feature a self-evaluation question on the treatment of gastric cancer. And we begin by reading the question stem. A 53-year-old Hispanic woman presents to her primary care physician after noticing black tarry stools for the last three weeks, and complains of mild fatigue. A stool guaiac test is performed in the office, and is found to be hemoccult positive. Her laboratory tests were notable for a white blood cell count of 6,400, a hemoglobin of 9.2, and hematocrit of 27.3%, with platelets of 653. The mean corpuscular volume was 77, blood urea nitrogen was 40, and creatinine was 1.3. A CT scan of the chest, abdomen, and pelvis was performed with IV contrast, and was notable only for nonspecific thickening of the gastric fundus. She was referred to a gastroenterologist, who performed an esophagogastroduodenoscopy, or EGD, which revealed an ulcerative mass along the greater curvature of the gastric fundus, with no evidence of active bleeding. This lesion was biopsied, and the pathology results confirmed adenocarcinoma, with signet ring cell features. A subsequent staging PET scan did not reveal any evidence of metastatic disease. What is the most appropriate next step in the management of this patient? Choice A, recommend subtotal gastrectomy. Choice B, recommend neoadjuvant therapy using epirubicin, oxaliplatin, and capecitabine, or EOX. Choice C, recommend endoscopic ultrasound. Choice D, recommend palliative radiation to control the bleeding. Or choice E, start the patient on oral iron after transfusion of two units of blood. [MUSIC PLAYING] In order to determine the appropriate treatment plan, we first need to know the local staging of the tumor based on endoscopic ultrasound, or EUS. Therefore, the answer would be choice C. Based on the findings of the endoscopic ultrasound, the next step for management can be better determined, whether it be endoscopic mucosal resection, surgical resection, or neoadjuvant chemotherapy with or without radiotherapy. Briefly the rationale for the other choices presented in this question do not represent the most appropriate therapy for the following reasons. Subtotal gastrectromy should not be entertained until staging endoscopic ultrasound is completed. If the lesion is a T1A lesion and amenable to endoscopic mucosal resection, then that would be more appropriate. Whereas if the lesion is a T4 lesion, with or without local regional adenopathy and ultrasonic evaluation, neoadjuvant therapy with EOX would be more appropriate. As for choice D, palliative radiotherapy is not indicated, as there is no active or uncontrollable bleeding, and there is no evidence of distant disease. Lastly, choice E, starting the patient on oral iron after transfusion of two units of blood is incorrect, because this patient doesn't warrant transfusion at this time, as she is asymptomatic other than mild fatigue. Thank you for listening to this week's episode of ASCO University Weekly Podcast. For more information on the treatment of gastric cancer, including opportunities for self-evaluation and board review, visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING] 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.