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Dr. Shaalan Beg and Dr. David Wang discuss key abstracts in GI cancers from the 2025 ASCO Gastrointestinal Cancers Symposium, including major advances in CRC, neoadjuvant approaches in esophageal cancer, and innovative studies on ctDNA. TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas. Today, we're bringing you some key highlights from the 2025 ASCO Gastrointestinal Cancers Symposium, and I'm delighted to be joined by the chair of GI25, Dr. David Wang. Dr. Wang is a GI medical oncologist at the University of Michigan. Our full disclosures are available in the transcript of this episode.  Dr. Wang, thanks for coming on the podcast today. Dr. David Wang: Well, thank you. It's a pleasure to be here. Dr. Shaalan Beg: GI25 featured major therapeutic advances across the spectrum of GI malignancies, and it was exciting to hear about innovations and novel approaches that are shaping the future of our field. Before we start talking about specific abstracts, could you share some of your key highlights from the meeting? Dr. David Wang: Sure. Our theme this year was “Breaking Boundaries to Enhance Patient Centered Care.” Past years' themes have focused more on precision oncology, but we wanted to broaden our focus on patients and to be more holistic, which kind of led us into some of the Intersection [sessions] that we had. Each day started with a different Intersection. The first one was “Emerging Therapies in GI Cancers”, where invited speakers talked about bispecific antibody drug conjugates, theranostics, CAR T and other cell-based therapies. The second day was on “Personalized Risk Assessment for GI Cancers,” and this included looking at polygenic risk scores for colorectal cancer, microRNAs and liquid biopsies such as exosomes and pancreatic cancer and non-endoscopic screening modalities in esophageal cancer. And on our final day, we wanted to talk about “Integrative Oncology and Integrative Medicine,” looking at evidence-based uses of acupuncture and supplements in patients who are receiving treatment for cancer, mindfulness-based practices and exercise. And of course, we had a fantastic keynote talk by Dr. Pamela Kunz from the Yale School of Medicine titled, “Disrupting Gastrointestinal Oncology: Shattering Barriers with Inclusive Science.” She highlighted the intersection of science, patient care, and health and gender equity. And I would encourage your podcast listeners to access the lecture in ASCO's Meeting Library if they haven't yet had a chance to hear Dr. Kunz's wonderful lecture.  We were really happy this year because the attendance hit a new record. We had over 5,000 people attend either in person or virtually from their home or office, and we had almost 1,000 abstracts submitted to the meeting, so these were either record or near record numbers. We offered a lot of different networking opportunities throughout the meeting, and attending found these to be incredibly rewarding and important and this will continue to be an area of emphasis in future meetings. Dr. Shaalan Beg: Let's take a deeper dive into the exciting studies presented at GI25. The late breaking abstract LBA143 was CheckMate-8HW. This was the first results of NIVO + IPI versus NIVO monotherapy for MSI-high metastatic colorectal cancer. What are your thoughts about this study? Dr. David Wang: Yeah, so we know that colorectal cancer patients with MSI-high tumors don't necessarily respond well to chemotherapy. And we were fortunate because last year CheckMate-8HW actually looked at two different arms – so this was NIVO + IPI compared to standard of care chemotherapy and showed its very significant improvement in median progression-free survival. And that was actually published in the New England Journal of Medicine back in November of 2024. This year's presentation actually focused now on NIVO + IPI versus NIVO monotherapy. And as you know IPI+NIVO can be quite toxic. So this was an important analysis to be done. So we know that NIVO is definitely more easily tolerated. So what was interesting was that the 2-year and 3-year progression-free survival not surprisingly favored IPI+NIVO and this was statistically significant. And the overall response rate was also better with IPI+NIVO versus NIVO alone. I know we're always concerned about toxicities and there were higher grade 3 and 4 toxicity incidences in the combination arm versus the monotherapy arm, but overall, only about 28 additional events in several hundred patients treated. So I think that's well-tolerated. Our discussant Dr. Wells Messersmith actually said that, with this new data, he would consider doing combination immunotherapy in any patient that presented in the front line with MSI-high or deficient mismatch repair colorectal cancer that was metastatic. Dr. Shaalan Beg: One of the focuses for directing first-line therapy for colorectal cancer has been right and left sided colon cancer because we know these are two different cancers with their own unique molecular subtypes. We heard on Abstract 17, the DEEPER trial, the final analysis of modified FOLFOXIRI plus cetuximab versus bevacizumab for RAS wild-type and left sided metastatic colorectal cancer. How do you summarize the findings of this study and what should our readers be aware of? Dr. David Wang: Interestingly, this was a phase 2 study and the emphasis of the abstract was actually a subgroup analysis of those patients with RAS wild-type and BRAF wild-type as well as left sided cancers. So, I think the entire study enrolled 359 patients, but the analysis that was discussed at the meeting really focused on 178 patients that fit that characteristic. Very similar to what we've seen in prior studies, left-sided tumors have better response to cetuximab versus bevacizumab. And if you flip it so that you now are looking at right sided tumors, targeting EGFR is actually detrimental. The depth of response was better with cetuximab in these left sided RAS and BRAF mutant tumors. And so the lead author actually suggested that this could be a new first-line standard of care. And the question is, is there a benefit of doing this triple agent regimen with modified FOLFIRINOX? We know there's a lot more toxicity with that. Not clear that there's a benefit for that over FOLFOX, maybe in younger patients that could tolerate it. When our discussant, again Dr. Wells Messersmith, spoke about this, he said that, in his practice he would, again, favor cetuximab over bevacizumab in combination with chemo, these left-sided RAS and BRAF wild-type tumors, but that he would actually prefer a doublet versus a triplet chemo regimen, and that is consistent with the current NCCN guidelines. Dr. Shaalan Beg: Another area where colorectal cancer has been a wonderful model to study new technology has been in the area of circulating tumor DNA (ctDNA). And the BESPOKE CRC trial is looking to see if ctDNA can inform adjuvant treatment decisions for stage II and III colorectal cancer. And in Abstract 15, we heard final results of the BESPOKE CRC sub-cohort. What were the findings there? Dr. David Wang: BESPOKE CRC is another one of these important ctDNA studies. It was an observational study, not a randomized trial, but it did provide a lot of different insights to us. We know that there were over 1,700 patients enrolled, and so it was reported that this is the largest ctDNA study in colorectal cancer performed in the United States. And they were able to analyze over 1,100 patients.  Some of the key findings were that postoperative adjuvant therapy management decisions actually changed in 1 out of 6 patients, so that's pretty significant. In terms of surveillance, we know that patients who have ctDNA positivity, this is prognostic of recurrence. In terms of patients who have positive ctDNA post-surgery, it looked like, at least in this observational study, the majority of patients who received any benefit were those who had positive ctDNA. So adjuvant therapy, even in stage II and stage III patients seemed to only benefit those patients who have positive ctDNA. I think that does raise the question, and this also was brought up in the discussion, which is “Can we de-escalate adjuvant therapy in terms of patients who are ctDNA-negative post-op?” And Dr. Richard Kim from Moffitt felt that we are not yet there. Obviously, we need randomized control trials where we are taking ctDNA results and then randomizing patients to receive adjuvant or non-adjuvant to really know the difference.  Other questions that come up with use of ctDNA include: What do you do with these patients who turn positive? This study for BESPOKE actually followed patients out to two years after surgery. So what you do with a positive ctDNA result wasn't really clear. It seems to suggest that once you turn positive, patients go on to more intensive surveillance. You know, again as an observation, patients who did turn positive were able to go to metastasis-directed therapy much more quickly. And again, this was supposedly to improve their curative intent therapy. And I think the other question that has been brought up all the time is, is this really cost effective? Patients want to know, and we want to give patients that information, but I think we're still stuck with what to do with a positive ctDNA level in a patient that's on surveillance because no randomized control studies have actually suggested that we need to start systemic therapy right away. Dr. Shaalan Beg: Yeah. And I guess in terms of practice informing or practice changing, these results may not give us a clear answer. But because a lot of patients are asking for these tests, it does give us some real world experiences on what to expect in terms of conversion of these positive into negative and the outcome so we can have a shared decision making with our patients in the clinic and then come up with a determination on whether ctDNA for molecular residual disease is something which would be worthwhile for the care of our patient. But more to come, I guess, in coming years to answer different problems around this challenge. Dr. David Wang: Yes, I agree. Dr. Shaalan Beg: The BREAKWATER trial looked at the use of encorafenib, cetuximab and chemotherapy for BRAF V600E-mutant metastatic colorectal cancer. We've covered this combination for a second- third-line treatment in metastatic colorectal cancer previously. Abstract 16 from GI25 was evaluating the use of this regimen in the first-line space. Everyone was looking forward to these results, and what did the investigators present? Dr. David Wang: I think this is, as you mentioned, a nice follow up to later lines of therapy where Dr. Kopetz from MD Anderson pioneered use of encorafenib, cetuximab and binimetinib in the BEACON trial. Everybody was kind of curious what would happen now if you use encorafenib plus cetuximab plus chemotherapy in the first-line setting. And so this is an interim analysis that was pre-planned in the phase 3 open label BREAKWATER trial. And even though there were three arms, and so the three arms were encorafenib plus cetuximab, encorafenib plus cetuximab plus FOLFOX, or standard of care chemo, only two arms were presented in the abstract. So basically looking at encorafenib plus cetuximab and FOLFOX-6 versus standard of care therapy, and the overall response rate was statistically significant with a 60.9% overall response rate encorafenib plus cetuximab plus chemo arm versus standard of care chemo was only 40%. The interim overall survival also was different. It was 92% versus 87% at 6 months and 79% versus 66% at 12 months, again favoring the chemotherapy plus encorafenib plus cetuximab. In terms of the statistics, the p was 0.0004. However, the pre-plan analysis required the p-value to be 1x10 to the -8. And so even though this looks really good, it hasn't quite met its pre-specified significance level. The good thing is that this is only interim analysis and the study is ongoing with future analysis planned.  So the real question is: Does it matter when we actually use this regimen? We know that the regimen's approved in the second third-line setting. What about in the first line? And there was some preclinical data that the discussant reviewed that shows that patients actually benefit if this is done in the first-line setting. For example, there was some preclinical data showing that even FOLFIRI, for example, can upregulate RAS, which would make tumors more resistant to this combination. This was thought to be practice-changing in a patient that has B600E showing up treatment naive that we should probably consider this regimen. And actually this did receive accelerated FDA approval about a month ago. Dr. Shaalan Beg: Yeah, and for what it's worth, I put up a Twitter poll asking my Twitter followers on how the BREAKWATER trial results will change their approach for newly diagnosed BRAF mutated colorectal cancer. We got 112 responses; 72% said that they will incorporate encorafenib, cetuximab, FOLFOX for their frontline BRAF mutated patients. But 23% said that they would like to wait for overall survival results. Dr. David Wang: Wow, that's interesting. They really want that 1x10 to the -8. Dr. Shaalan Beg: I guess so. All right. Let's change gears and talk about esophageal cancer. LBA329 was the SCIENCE study which presented preliminary results from a randomized phase 3 trial comparing sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy for neoadjuvant resectable locally advanced squamous esophageal cancer. Where are we in this space? Dr. David Wang: Okay. So, yeah, this was an interesting trial. Again, just to set the context, esophageal squamous cell carcinoma is more prevalent in Asia. And the study sites as well as the patients were mostly from Asia. So this was again a phase 3 trial with interim results. They only rolled 146 out of the planned 420 for this interim analysis. And yeah, they're using immune checkpoint inhibitor that we don't use in the United States, sintilimab, combined with their two standards of neoadjuvant therapy, either chemotherapy, which is more common in Asia, or or chemoradiation, which is more common in the US and Western Europe, versus chemoradiation. And so they actually had two primary endpoints, but only were reporting one. So their two primary endpoints were pathCR and the other one was event-free survival. The event-free survival, again, was not reported at the meeting.  What they found was that in terms of pathCR rate, if you take the two arms that are really informative about that, chemoradiation plus sintilimab versus chemoradiation alone, the pathCR rate was 60% versus 47%. We know that chemo alone doesn't induce as much of a pathCR rate, and that was 13%. So it was found that the delta in terms of pathCR between the chemoradiation arms, one with sintilimab and one without, was significant. And this actually confirms data again from Asia, like for the ESCORT-NEO trial where it used another immune checkpoint inhibitor pembrolizumab in addition to neoadjuvant chemo.  So as our discussant for this abstract said, yes, we know that radiation combined with chemotherapy improves pathCR rates, but we have recent data from the ESOPEC trial, we don't know that that necessarily will translate to overall survival. So again, waiting for additional enrollments and longer term follow up before incorporating this into clinical care here. Dr. Shaalan Beg: So David, how do the results of the SCIENCE trial compare with our practice in the United States and ongoing studies asking questions for neoadjuvant therapy for esophageal carcinoma in the United States? Dr. David Wang: I think obviously immune checkpoint inhibitor in the new adjuvant setting is important. Jennifer Eads at UPenn is running that EA2174 which is looking at chemoradiation plus or minus nivolumab, and then in non-pathCR responders randomized to adjuvant nivolumab per CheckMate 577 or nivolumab with intensification adding ipilimumab. We know that the ESOPEC trial just came out, and was published actually during the meeting, and that really focuses on adenocarcinomas. So adenocarcinomas of the GE junction, distal esophagus, now, we would probably treat very similarly to gastric using perioperative FLOT. However, the standard in the US for esophageal squamous cell carcinoma remains neoadjuvant chemoradiation. We know that squamous cell carcinomas are more exquisitely sensitive to radiotherapy. And then obviously in those patients who don't achieve a pathologic complete response, the expectation would be that they would go on to receive nivolumab per CheckMate 577. Again, the thought is that these tumors are more sensitive to immunotherapy given their higher incidences of mutational changes. And so again, this kind of goes along with the positive results seen in the SCIENCE trial that we just discussed with sintilimab but also EFFECT-neo with pembrolizumab. Obviously, we await the results of Jennifer's trial. Dr. Shaalan Beg: And the last abstract I was hoping we could get your perspective on was Abstract 652, which is a Phase 3 study of everolimus plus lanreotide versus everolimus monotherapy for unresectable or recurrent gastroenteropancreatic neuroendocrine tumors, the STARTER-NET trial. What were the results of this study? Dr. David Wang: So, I just want to give a shout out because we did have a session at this year's GI ASCO that looked at more rare tumors. So appendiceal tumors, neuroendocrine tumors, those kinds of things. So again, I would encourage your listeners to listen to that session if they have interest in that. Another type of rare tumor was adenosquamous tumors.  But in terms of the STARTER-NET trial, this was again an interim analysis of his phase 3trial and it was looking at combining everolimus plus lanreotide versus everolimus. So we know that in pancreatic-gastric neuroendocrine tumors, if you have low Ki-67, a well differentiated tumor, that the standard of care really is a somatostatin analog, and sometimes if they're more aggressive, we kind of consider molecular targeted therapy with everolimus. This was asking the question of whether we should do the combination on the frontline. And what was interesting is in this study, the patients were actually more of a poor prognostic set. So they had Ki-67 up to 20% or these were patients that actually had multiple liver lesions. And what they found was a median for progression free survival was improved with a combination out to 29.7 months versus 11.5 months with the somatostatin analog alone, and that the overall response rate was 23% versus 8.3%, again, favoring the combination. If you looked at subgroup analysis, it was actually those patients who had Ki-67 greater than 10%, so the more aggressive tumors, or those with diffuse liver lesions that had the most benefit. So I think that would be the patient population I would consider this new combination with using would be those patients again with poorer prognosis neuroendocrine tumor phenotype. Dr. Shaalan Beg: Thank you very much, Dr. Wang, for sharing your insights with us today and your great work to build a robust GI Cancers Symposium this year. Dr. David Wang: Well, thank you. I mean that really is a cooperative effort. We appreciate all the members of the GI25 Program Committee as well as the ASCO staff that just made it an outstanding meeting. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed today on the transcript of this episode.  Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: 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. Find out more about today's speakers:  Dr. Shaalan Beg @ShaalanBeg  Dr. David Wang Follow ASCO on social media:   @ASCO on Twitter  @ASCO on BlueSky ASCO on Facebook   ASCO on LinkedIn   Disclosures:  Dr. Shaalan Beg:  Employment: Science 37  Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine  Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals  Dr. David Wang: Honoraria:  Novartis Consulting or Advisory Role: Novartis, Cardinal Health, Bristol-Myers Squibb, BeiGene, Eisai  

Dr. Shaalan Beg and Dr. Arturo Loaiza-Bonilla discuss the potential of artificial intelligence to assist with patient recruitment and clinical trial matching using real-world data and next-generation sequencing results. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host for the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center in Dallas and senior advisor for clinical research at the National Cancer Institute. On today's episode, we will be discussing the promise of artificial intelligence to improve patient recruitment in clinical trials and advanced clinical research. Joining me for this discussion is Dr. Arturo Loaiza-Bonilla, the medical director of oncology research at Capital Health in Philadelphia. He's also the co-founder and chief medical officer at Massive Bio, an AI-driven platform that matches patients with clinical trials and novel therapies.  Our full disclosures are available in the transcript of this episode.   Arturo, it's great to have you on the podcast today.  Dr. Arturo Loaiza-Bonilla: Thanks so much, Shaalan. It's great to be here and talking to you today.  Dr. Shaalan Beg: So we're all familiar with the limitations and inefficiencies in patient recruitment for clinical trials, but there are exciting new technologies that are addressing these challenges. Your group developed a first-in-class, AI-enabled matching system that's designed to automate and expedite processes using real-world data and integrating next-generation sequencing results into the algorithm. You presented work at the ASCO Annual Meeting this year where you showed the benefits of AI and NGS in clinical trial matching and you reported about a twofold increase in potential patient eligibility for trials. Can you tell us more about this study?  Dr. Arturo Loaiza-Bonilla: Absolutely. And this is just part of the work that we have seen over the last several years, trying to overcome challenges that are coming because of all these, as you mentioned, inefficiencies and limitations, particularly in the manual patient trial matching. This is very time consuming, as all of us know; many of those in the audience as well experience it on a daily basis, and it's resource intensive. It takes specialized folks who are able to understand the nuances in oncology, and it takes, on average, even for the most experienced research coordinator or principal investigator oncologist, 25 minutes per trial. Not only on top of that, but in compound there's a lack of comprehensive genomic testing, NGS, and that complicates the process in terms of inability to know what patients are eligible for, and it can delay also the process even further.  So, to address those issues, we at Massive Bio are working with other institutions, and we're part of this … called the Precision Cancer Consortium, which is a combination of 7 of the top 20 top pharma companies in oncology, and we got them together. And let's say, okay, the only way to show something that is going to work at scale is people have to remove their silos and barriers and work as a collaborative approach. If we're going to be able to get folks tested more often and in more patients, assess for clinical trials, at least as an option, we need to understand further the data. And after a bunch of efforts that happened, and you're also seeing those efforts in CancerX and other things that we're working on together, but what we realize here is using an AI-enabled matching system to basically automate and expedite the process using what we call real-world data, which is basically data from patients that are actually currently being treated, and integrating any NGS results and comparing that to what we can potentially do manually. The idea was to do multi-trial matching, because if we do it for one study, yeah, it will be interesting, but it will not show the potential applicability in the real world.  So with all that background, the tool itself, just to give you the punchline of it, was proven highly effective in terms of efficiency. We were able to increase the number of potential matches, and not only that, but reducing the time to the matching. So basically, instead of spending 25 minutes, it could be done in a matter of seconds. And when you compound all that across multiple clinical trials, in this case, it was several sponsors coming together, we were able to reduce the manual effort of seeing patients and testing for clinical trials to basically 1 hour when it would have otherwise taken a ridiculous amount of time. And it was quantified as 19,500 hours of manual work, compared to 1 hour done by the system to uniquely match a cohort of about 5,600 patients that came into the platform. And this was across 23 trials. Now imagine if we can do it for the 14,000 clinical trials currently in clinicaltrials.gov.   So for us, this kind of was an eye-opening situation that if we can increase not only the efficiency but find even more trials by integrating comprehensive genomic testing, which in this case was a twofold increase in eligibility for clinical trials, that gives us not only the opportunity for optimized processes using AI but also a call to action that there is still a lot of under-genotyping. And I know American Cancer Society and ASCO and many others are working hard on getting that into fruition, but we need to have systems that remind us that certain patients are not tested yet and that can improve not only real patients, but the R&D and the process of innovation in the future. Dr. Shaalan Beg: Yeah, it's always an important reminder that even some of the highest impact IT solutions or AI solutions are most effective if they can be integrated into our normal clinical processes and into the normal workflow that we have in our clinics to help clinicians do their work quickly and more efficiently. Can you talk about how, over the last few years, the availability of NGS data in our electronic medical record (EMR) has evolved and whether that's evolving for the better? And what are some next steps in terms of making that data available at EMR so that such solutions can then pull that data out and do clinical trial matching?  Dr. Arturo Loaiza-Bonilla: Yes. So one of the things that we have seen over the last couple of years is because of the applicability of the 21st Century Cures Act, there is less “information blocking,” which is patients not being able to access their information in real time. Now, with the appearance of health exchanges, with patient-centric approaches, which is something that many innovators, including ours, are trying to apply, it's really becoming more relevant. So it's not only helping us to find the patients when they really need to get tested, but also is giving us the opportunity to put those patients into the right treatment pathway when found. Something that's still a challenge and I think we can work by being more collaborative once again – is my dream – is having these pre-screening hubs where no matter where you are in your cancer journey, you just go into that funnel and then are able to see, “Okay, you are in the second-line setting for non-small cell lung cancer, EGFR-mutated. Now, do you have a meta amplification, then you go for this study or this trial. Oh, you haven't been tested yet. You should get tested. You're a pancreas cancer patient who is KRAS wild type; well, there is a significant chance that you may have a biomarker because that's where most patients are enriched for.” So having that opportunity to at scale, just for the whole country, to get those patients access to that information, I think is crucial for the future of oncology. And I think you working at the NCI, more than most, know how the impact of that can help for those underrepresented patients to get more access to better treatment options and whatnot. And we can activate clinical trials as well in new models, decentralized models, adjusting time models, all those things can be leveraged by using biomarker testing in real time. Identification when the patient really needs a trial option or a medication option, because the data is telling us when to activate that in real time. Dr. Shaalan Beg: And identifying the patient for a potential clinical trial is one challenge. In oncology, given a lot of our trials, we are looking to enroll people at a specific time in their disease journey. So we call it first-line or second-line or third-line, becomes the next challenge. So just knowing someone has mutation number 1, 2, or 3 isn't enough to say they would be eligible for a second-line BRAF X, Y and Z mutation at a given trial. I've heard you talk a lot about this last-mile navigation for people once you've identified that they may be a soft match for a clinical trial. Can you talk about what you've seen in the ecosystem being developed on how AI is helping both clinics and patients navigate this last mile from the time they're identified for a clinical trial to the time they actually receive cycle 1, day 1? Dr. Arturo Loaiza-Bonilla: Yeah, absolutely. And that is such a critical point because, as you know, we have helped tons of patients getting trial options in thousands of cases. But even my own patients, I give them a report for trial options and they're like, “Okay, I still need help.” And we have been talking with ASCO, with the American Cancer Society, and many other very good teams, and what we see as an opportunity in technology here is leveraging those cancer journeys to know when the patient really has the opportunity to enroll in a trial, because this is a very dynamic environment. Not only the patient's condition changes because their cancer progresses, the hemoglobin changes, the cancer moves from one place to the other, and there's nuances in between, but also new medications are coming up, studies open and close, sites open and close.  So having this information as a hub, as what we call a command center, is the key to make this happen. And we can use the same tools that we use for Uber or for Instacart or whichever thing you want to do; it's already the same concept. When you need groceries, you don't need groceries every day. But Amazon gives you a ding that's like, “Well, I think you may be running out of milk,” because they already know how often you buy it, or just having the data behind the scenes of how typically these, in this case, patient journeys, may manifest based on the biomarker. So let's say a smoldering multiple myeloma is not the same across. One patient with biomarkers that make them very high risk, the risk of progressing to a multiple myeloma, first-line treatment-eligible patient is going to be much different than someone who has better risk cytogenetics. So using that tool to optimize the cancer journeys of those patients and being able to notify them in real time of new trial options, and also knowing when the patient really has that disease progression so there's a time of activation for trial matching again, the same way you get a credit score for buying a house, then you know exactly what options are in front of you at that very moment. And that is the last-mile component, which is going to be key. What we have seen that we feel is important to invest on, and we have invested heavily on it, is that until the patient doesn't sign the consent form for the clinical trial, that patient is completely unknown to most people. The site doesn't know them because they haven't been there, and they may be there, but they don't know about the options sometimes. But no one's going to invest in getting that patient to the finish line. There's a lot of support for patients on trials, but not before they enroll on trials. And we feel that this is a big opportunity to really exponentially grow the chances of patients enrolling in trials if we support them all the way from the very time they get diagnosed with cancer in any setting. And we can help that patient on a very unique journey to find the trial options using technology. So it's very feasible. We see it once again in many other equally complex tasks, so why not do it in oncology when we have all the bonafides across wanting to do this. Dr. Shaalan Beg: Can you give examples of where you are seeing it done outside of oncology that's a model that one can replicate? Dr. Arturo Loaiza-Bonilla: I mean, oncology is the toughest use case to crack. You have experiences with DCTs in the past and all that. So the big opportunities are for patients, for example, in psychiatry, when they need certain counseling and help. We see that also in medical devices, when people have diabetes and they really need a device specifically for that unique situation, or also for patients with cardiovascular risk that they can in real time get access to novel therapeutics. And that's how they have been able to enroll so quickly. And all these GLP-1 inhibitors, all those models are really almost completely decentralized nowadays in something that we can extrapolate for oncology once we have aligned the ecosystem to make it see them. This is something that we can really revolutionize care while we manage all the complex variables that typically come with oncology uses.  Dr. Shaalan Beg: I would imagine while you translate those learnings from outside of oncology into oncology, a lot of those processes will be human and AI combination activities. And as you learn more and more, the human component becomes a smaller fraction, and the technology and the AI becomes more of a component. Are you seeing a similar transition in the clinical trial matching space as well? Dr. Arturo Loaiza-Bonilla: Yes. So that's why people say humans are going to be replaced. They're not. Patients still want to see a human face that they recognize, they trust. Even family members of mine want to hear from me, even if they are in the top place in the world. What we can change with technology are those things that are typically just friction points. In this case, information gathering, collecting records, getting the data structured in a way that we can use it for matching effectively, knowing in real time when the patient progresses, so we can really give them the chances of knowing what's available in real time. And collecting the information from all these other stakeholders. Like, is the site open? Is the budget approved for that place? Is the insurance allowing the specific … do they have e-consent? Those things can be fully automated because they're just burdensome. They're not helping anyone. And we can really make it decentralized for e-consent, for just getting a screening. They don't need to be screened at the site for something that they're going to receive standard of care. We can really change that, and that's something that we're seeing in the space that is changing, and hopefully we can translate it fully in oncology once we are getting the word out. And I think this is a good opportunity to do so. Dr. Shaalan Beg: You talked about your dream scenario for clinical trial matching. When you think about your dream scenario as a practicing oncologist, what are the AI tools that you are most excited about making their way into the clinic, either wishful thinking or practically? Dr. Arturo Loaiza-Bonilla: I typically get feedback from all over the place on doing this, and I also have my own thoughts. But I always come to this for a reason. We all became physicians and oncologists because we like being physicians. We like to talk to patients. We want to spend the time. I tell folks in my clinic, I will see a thousand patients all the time as long as I don't have to do notes, as long as I don't have to place orders. But of course, they will have to hire 1,000 people ancillary to do all the stuff that we do.  If we can go back and spend all that time that we use on alert fatigue, on clicking, on gathering things, fighting insurance, and really helping align those incentives with clinical trials and biomarker testing and really making it a mankind or a humankind situation where we're all in this really together to solve the problem, which is cancer, that will be my dream come true. So I don't have to do anything that is clerical, that is not really helping me, but I want to use that AI to liberate me from that and also use the data that is generated for better insights. I think that I know my subject of expertise, but there's so many things happening all the time that it is hard to keep up, no matter how smart you are. If the tool can give me insights that I didn't even know, then leverage that as a CME or a board certification, that would be a dream come true. Of course, I'm just dreaming here, but it's feasible. Many of these ideas, as I mentioned, they're not new. The key thing is getting them done. The innovative part is getting stuff done, because I'm sure there's a gazillion people who have the same ideas as I did, but they just don't know whom to talk to or who is going to make it happen in reality. And that's my call to action to people: Let's work together and make this happen. Dr. Shaalan Beg: Well, Arturo, thanks a lot for sharing your insights with us today on the ASCO Daily News Podcast. Dr. Arturo Loaiza-Bonilla: Well, thank you so much for the time and looking forward to having more exchanges and conversations and seeing everyone in the field. Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find a link to the studies discussed today in the transcript of this episode. And if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: 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.   Find out more about today's speakers:  Dr. Shaalan Beg    @ShaalanBeg Dr. Arturo Loaiza-Bonilla @DrBonillaOnc   Follow ASCO on social media: @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures:    Dr. Arturo Loaiza-Bonilla: Leadership: Massive Bio Stock and Other Ownership Interests: Massive Bio Consulting or Advisory Role: Massive Bio, Bayer, PSI, BrightInsight, Cardinal Health, Pfizer, Eisai, AstraZeneca, Regeneron, Verily, Medscape Speakers' Bureau: Guardant Health, Bayer, Amgen, Ipsen, AstraZeneca/Daiichi Sankyo, Natera   Dr. Shaalan Beg:    Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen    Speakers' Bureau: Sirtex    Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics    Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune

Dr. Shaalan Beg and Dr. Arjun Gupta discuss the rationale behind treatment breaks and assess the pros and cons based on feedback and data from patients with advanced-stage gastrointestinal cancers. TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center in Dallas and senior advisor for clinical research at the National Cancer Institute. I'll be your guest host for the podcast today.  On today's episode, we'll be discussing treatment holidays in GI cancers. Treatment holidays, also known as drug holidays, are increasingly being discussed in clinical practice and involve voluntarily halting treatment for a duration determined by a health care provider if believed to be beneficial for a patient's well-being. We'll address the rationale behind treatment holidays and explore their potential risks and benefits. Joining me for this discussion is Dr. Arjun Gupta, a GI medical oncologist and health services researcher at the University of Minnesota. Dr. Gupta's research on treatment-related time toxicity has explored the benefits of taking a break from treatment.  Our full disclosures are available in the transcript of this episode.  Arjun, it's great to have you on the podcast today. Dr. Arjun Gupta: Thanks, Shaalan. It's a joy to be here. Dr. Shaalan Beg: Your research at the intersection of oncology, supportive care, and care delivery is extremely interesting and important in today's day and age. And you've done extensive work on the concept of time toxicity in cancer treatment. So as we think about these discussions in the clinic on treatment holidays and we talk about risks and benefits, I was hoping that you could help explain the concept of time toxicity in cancer treatment and what our listeners should remember from this. Dr. Arjun Gupta: Sure. So time toxicity is simply the time commitments that cancer care imposes on people with cancer and their loved ones, and the burden that comes along with these commitments. When we specifically think about time toxicity associated with a particular cancer treatment, such as chemotherapy, it's the time costs of pursuing, receiving, and recovering from cancer treatment. Now, we have to acknowledge that much of cancer care is essential. We need blood tests to monitor organ function, we need chemo to shrink tumors, and we need a caring oncologist to break bad news. But we have to remember that oncology care is delivered in an imperfect world. Appointments that should take 10 minutes can take 5 hours. People can have uncoordinated appointments, so they're coming to the clinic 3, 4, 5 times a week. And this affects, of course, not only the patient themselves but also their informal care partners and the entire network around them. And this cancer care can completely consume people's lives, leaving no time for rest, recovery, or pursuing joyful activities.  We interviewed patients and care partners in some qualitative work, and this was specifically people with advanced-stage gastrointestinal cancers. And we asked them what cancer care was like, and some of the words will shock you. People said things like, “It's like being on a leash.” “My life is like being on an extended COVID lockdown.” “Cancer is a full-time job.” A very experienced oncologist said, “It's like being on call. You may or not get called into the hospital, but you need to always be available.” And so this concept of time toxicity really applies to all people with cancer, but perhaps most so for people with advanced-stage, incurable cancer, when time is limited and when treatment regimens are perhaps not offering massive survival benefits. And in some cases, the time costs of pursuing the treatment can even overtake the very marginal survival benefit offered by the treatment. Dr. Shaalan Beg: This is particularly relevant for gastrointestinal cancers that, even in the world of advanced cancers, are highly burdensome in terms of their symptoms and the concept of being on call, whether you're a patient or a caregiver, and the burden that it has, I think will resonate with a lot of us, that it's always in the back of our mind on what if X, Y or Z were to happen? In the FOCUS4-N trial, a randomized trial from the UK, investigators assessed whether taking a treatment holiday for maintenance therapy for metastatic colorectal cancer would have a detrimental effect on progression free survival, overall survival, tolerability and toxicity. It looks like the study found that these decisions regarding maintenance therapy should be individualized, but there were not major differences in outcome. Can you comment on this and what applications that has for us in the clinic?  Dr. Arjun Gupta: Sure. But before diving into the FOCUS4-N clinical trial, I just wanted to share a story from the clinic yesterday. It happened in my clinic yesterday, but I'm sure it happens to thousands of patients across the world every single day. So it was the first visit for a patient with stage 4 colon cancer, and they had polymetastatic disease with disease in the lungs and the liver, no actionable biomarkers, and so very likely to be incurable. And so we discussed the usual port and palliative care appointments and chemotherapy backbone, and doing this every 2 weeks, and then doing scans after 4 to 6 doses of chemo to see how the cancer has responded. And then the patient looks up and asks that question, “Okay. So when does this end? When are we done? Do I need to do this forever and the rest of my life?” These are just such innocent and hopeful questions, because the truth is, there is no established end date. But I shared this story that right off the bat, people are looking for breaks. They've not even started chemo, they've not experienced physical or financial or time toxicity, but just psychologically, being on chemo long-term or forever is a very, very hard adjustment.  And so it's in this context that we should look at the FOCUS4-N clinical trial, which was a sub- study of a larger umbrella trial investigating whether continuing on maintenance chemo with oral capecitabine versus taking a treatment break from chemo affected the progression-free survival in people with metastatic colorectal cancer who had disease control after 4 to 6 months of upfront chemotherapy. So they randomized approximately 250 people. These people had largely been treated with FOLFOX or FOLFIRI. Most did not receive a biologic, and approximately half had partial response and half had stable disease. And then they did scans on these patients every two months or so. And the primary endpoint was progression free survival. The median PFS was approximately 4 months in the capecitabine arm and 2 months in the no treatment arm. Of course, as expected, side effects were higher in the capecitabine arm. But impressively, the overall survival was not different between these two arms. So what we're seeing here is that after this period of 4 to 6 months of intensive chemo, if we take a chemo break versus we get some oral chemotherapy, it may affect how quickly the cancer grows on scans, but it maybe does not affect how long patients live.  Now, how do these data apply for an individual patient? Now, these are incredibly nuanced and personal decisions and patients can and should choose what aligns best with their values. In some work done by Dr. Mike Brundage and colleagues in Canada, they asked 100 people with advanced cancer to consider hypothetical scenarios where a new treatment did not increase the overall survival, but potentially increased the progression free survival at the cost of some physical and other toxicities. And then they asked patients if and what PFS thresholds they would accept for this treatment. And around half of patients said no matter how big the PFS is, we do not want to accept the treatment because it causes some toxicity if I'm not going to live longer. Around a quarter of patients said that if the drug elongated progression free survival by three to six months, I would take it, because that's valuable to me even if I don't live longer. But surprisingly, 1 in 6 patients said that they would accept a treatment with no PFS benefit and no overall survival benefit, even at the cost of side effects. And there was a spectrum of reasons for these preferences that they maybe had the battle narrative that “I want to be a fighter, and I don't want to have any regrets,” just showing how complex people's attitudes and values can be. So the point is that continuing on maintenance treatment versus not doing it is not wrong. The point is we often don't even have these data to offer treatment breaks to patients so that they can make decisions that align with their goals.  So I think that's the biggest takeaway from the FOCUS4-N trial for me is that we have some hard data now to guide patients [FOCUS4-N Editorial]. Now, strictly speaking, when I'm talking to a patient about these data, doing oral capecitabine in 3-week cycles may not feel like much. It's perhaps a visit every 3 weeks for blood work and for meeting someone from the oncology team. There are no IV drugs given. If one does well, this might literally be one visit every 3 weeks. But we have to consider that things rarely go as smoothly as we plan them to. For someone living 100 miles away and having diarrhea and needing IV fluids, they may require 3 to 4 clinic visits for labs and monitoring.  In the FOCUS4-N trial, 50% of patients on capecitabine had at least one treatment delay, denoting some toxicity. In a different but similar CAIRO3 clinical trial that tested capecitabine and bevacizumab, 10% of patients had to discontinue treatment due to toxicity. And so it's important to remember that what might seem a simple and low burden to us may be very burdensome to patients. In some work that we've done ourselves [published in The Oncologist], even a single simple appointment to a clinic, such as a lab test, often ends up taking patients hours and hours. So I think it's all of this that we have to consider when we present these data to patients.  Dr. Shaalan Beg: You've talked about the FOCUS4-N trial, you mentioned the CAIRO3 study as well. How do you see this playing in the clinic? Somebody may be looking to attend a child's wedding or a notable birthday or a trip with the family, and you have the data from these trials supporting you. What are the patient factors in terms of their disease factors, patient factors that you think of when you recommend such a treatment break to a patient? Or, let me flip that over. Who would be a patient that you would be uncomfortable offering a treatment break for with metastatic colorectal cancer?  Dr. Arjun Gupta: Yes, I think disease characteristics are a crucial consideration when we consider who we're even offering these treatment breaks to. I think, number one, is the overall disease burden, and if there's any critical visceral disease and how that's responded and how much it's responded to the upfront chemotherapy induction. I think patients where we're worried about having several sites of bulky disease, some that have not responded as well, I think we have to be very, very careful considering complete chemotherapy breaks. In the FOCUS4-N trial, in subgroup analysis, patients who had stable disease tended to not benefit as much from the chemotherapy break, perhaps indicating that it's really people whose disease is responding, who are doing well, who don't have as much disease burden, who may be better served by these treatment breaks. Dr. Shaalan Beg: Fantastic. I think that provides very good direction for our listeners on how they can apply the results of these trials in their clinic.  So we've talked about treatment breaks as a way to give people their time back and to reduce time toxicity. What are other treatment strategies that you have seen deployed to reduce the burden of receiving cancer treatments in general? Dr. Arjun Gupta: You specifically asked about treatment strategies, so I'll start with that before moving to more broad interventions. We actually interviewed patients and care partners to ask them this question, and one of the things that they said was having prospective information from their oncology care team just about what my expected burden was going to be. So I think people recognize that they need oncology care and the clinicians are trying to help them and it's a broken system, but just knowing that 1 in 4 days will be spent with health care contact or not, or you will spend two hours arguing on the phone with a payer, for example, preparing and supporting people for these burdens is very important. There are obviously some alternative treatment schedules. Certain chemotherapies can be given less frequently now. So if you look at cetuximab in GI cancers, for example, when the initial trials were done, it was given every week, but now we more and more use it every two weeks. And it might not seem like much, but it can open up an entire week for a patient when they can think that I don't need to go in this week at all. So these are just some minor adjustments that we can make in the clinic.  But patients often highlight things that may perhaps not be in the direct control of the oncologist, but in the direct control of us as an oncology community. And perhaps the most frequently cited suggestion was having more care coordination and navigation services. So patients really requested more flexibility in the site of care: “Can I come closer to home?'' In the timing of their care, ‘'Can I come in at 2:00 PM after I get childcare instead of coming in at 9:00 AM?” They really requested cluster scheduling or having appointments on the same day, if possible, instead of taking up Monday, Tuesday, Wednesday, Thursday, coming in so many times. And all of this could potentially be achieved by having a designated care coordinator, someone working directly with the patient and their care partner. And then some patients also highlighted the benefits of telemedicine and home-based care, where they were able to be home more.  But we have to also recognize that those things are not universally good and often can increase burdens on the patients and care partners. Also, I wanted to highlight some feedback we received from oncology clinicians. We asked a variety of oncology clinicians, including nurses, APPs, physicians, schedulers, and social workers, what they thought were the causes of patients' time burden. You'll be surprised to hear that when they started talking about patients' time burdens, they slowly started to talk about their own time burdens. And they said, ‘‘We really want to help people, but we're just doing prior authorization and spending hours on the electronic medical record. And please fix my own time toxicity, and I will fix the patients' time toxicity,” which I thought was very profound because I think everybody who goes into medicine goes into it for the right reasons, and we end up not providing perfect care, not because of us, but because of the system. I take this as a very, very positive sign and as a hope for change. Dr. Shaalan Beg: What inspired you to focus on this topic and your research?  Dr. Arjun Gupta: So I personally just hate waiting at the doctor's office. But yes, it's also been wise mentors, including you, Shaalan, during residency and fellowship, who always told me to keep my ear to the ground and listen to patients. And in full disclosure, time toxicity, and what we've done with it recently, it's nothing new. It's been around for decades. And I think our research group has just sort of named it and shamed it, and now more and more people are starting to think about it.   But I can point to two specific instances that I think of. One was when I was starting fellowship in 2018, I read a piece by Dr. Karen Daily in the Journal of Clinical Oncology, where she quoted Henry Thoreau and said, “The price of anything is the amount of life, or time, that you exchange for it.” And it really struck a chord with me, entering the oncology discipline and seeing what people with cancer go through.   And then the second instance is, I remember my granddad, who was perhaps the most formative person in my life. We were very, very close. And when I was about to enter medical school, he was undergoing chemotherapy for lymphoma. The image that's imprinted in my head is of him putting ketchup on gulab jamun. And I can see Shaalan salivating. But for the listeners who may not know, gulab jamun is an Indian sweet made out of milk, flour, sugar, ghee, molded into balls, deep fried and then served in sugar syrup. And my granddad could not taste anything. He could not taste gulab jamun. All he could taste was ketchup. And so he would put ketchup on everything. And at his oncologist visits when I would accompany him, they would discuss the good news about the cancer shrinking and there being a response, and he was happy, but he could just not taste his gulab jamuns. And it made me realize very early on that the tumor is not the only target.  Dr. Shaalan Beg: What a wonderful story. I think those are really hard to measure, quantify, and when patients do bring those stories into the clinic, I think you realize that you have a very special connection with those patients as well, and it does help us as clinicians give personalized advice. So thanks for sharing.  Arjun, thanks for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Arjun Gupta: Thanks so much for having me, Shaalan. Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the studies discussed today in the transcript of the episode. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: 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.   Find out more about today's speakers:  Dr. Arjun Gupta @guptaarjun90   Dr. Gupta's Research on Time Toxicity: ·      The Time Toxicity of Cancer Treatment, JCO ·      Consuming Patients' Days: Time Spent on Ambulatory Appointments by People With Cancer, The Oncologist ·      Evaluating the Time Toxicity of Cancer Treatment in the CCTG CO.17 Trial, JCO OP ·      Patients' considerations of time toxicity when assessing cancer treatments with marginal benefit, The Oncologist ·      Health Care Contact Days Experienced by Decedents With Advanced GI Cancer, JCO OP ·      Health Care Contact Days Among Older Cancer Survivors, JCO OP Dr. Shaalan Beg    @ShaalanBeg   Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures:   Dr. Arjun Gupta: Employment (An Immediate Family Member): Genentech/Roche   Dr. Shaalan Beg:    Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen    Speakers' Bureau: Sirtex    Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics    Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune

Dr. Shaalan Beg highlights practice-changing studies in GI cancers featured at the 2024 ASCO Annual Meeting, including the ESOPEC trial in esophageal adenocarcinoma and durable responses to PD-1 blockade alone in mismatch repair-deficient locally advanced rectal cancer. TRANSCRIPT Geraldine Carroll: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Shaalan Beg, an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center. Dr. Beg will be discussing practice- changing abstracts and other key advances in GI oncology that were presented at the 2024 ASCO Annual Meeting. His full disclosures are available in the transcript of this episode.  Dr. Beg, thanks for being on the podcast today.  Dr. Shaalan Beg: Thank you for having me. Geraldine Carroll: Let's begin with LBA1, the ESOPEC trial. This was featured in the Plenary Session, and this study compared two treatment strategies for locally advanced esophageal adenocarcinoma that could be treated with surgery. The strategies include the CROSS protocol, which consisted of chemoradiotherapy before surgery, and the FLOT protocol of chemotherapy before and after surgery. Can you tell us about this practice-changing study, Dr. Beg? Dr. Shaalan Beg: Yes. According to this study, perioperative chemotherapy with FLOT was better than neoadjuvant therapy with chemoradiation and carbo-taxol for people with adenocarcinoma of the esophagus. There were 438 patients enrolled on this phase 3 study. R0 resection rates were fairly similar across both groups. The PCR rates were a little higher on the FLOT group. But when you look at the median overall survival difference, 66 months in the FLOT group versus 37 months in the CROSS group, 3-year survival was 57% versus 50% favoring FLOT therapy as well.  So a couple of caveats on this clinical trial, because the first thing to note is that the standard treatment for this disease has evolved because we now don't only give CROSS chemoradiation, we also give immunotherapy after the completion of chemoradiation for this group of patients. And in this study, since it predated that standard of care, patients did not receive immunotherapy. But having said that, the take home for me here is that chemotherapy is better than chemoradiation for this group of patients, recognizing the fact that 1) they only enrolled adenocarcinoma patients, and 2) patients with high T stage were not included. So the folks with high T stage would be those who we would expect would benefit from the radiation aspect. So my take home here is that more chemotherapy is better in the perioperative space. Radiation should be considered for individuals who need more local control. But in general, I think we're going to see us moving more towards chemotherapy-based regimens with FLOT for this group of patients. Geraldine Carroll: Great. So moving on to rectal cancer, in LBA3512, investigators reported durable, complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer. Can you tell us more about the promising durable responses that occurred in this trial?  Dr. Shaalan Beg: On first glance, seeing that immunotherapy has good activity in patients with mismatched repair deficient rectal cancer isn't really headline breaking news anymore. We've known about this activity for this group of patients for many years. Earlier at ASCO, the investigators presented early results of this compound for people receiving six months of dostarlimab therapy for people with mismatched repair deficient, locally advanced rectal cancer, and showed that they had a very high complete response rate. At that time, it generated a lot of interest and there was a lot of curiosity on whether these outcomes will be sustained. We don't know other characteristics of their biologic status and whether this was some sort of reflection of the patients who are selected or not.   So here in this presentation at ASCO 2024, they did come back to present follow-up data for people with mismatch repair deficient colorectal cancer, having received 6 months of dostarlimab. Forty-seven patients had been enrolled, and the 41 patients who had achieved a clinical complete response continued to have disease control with no distant metastases. So that's very compelling information. There were no additional serious adverse events greater than grade 2 that they saw, and they did follow circulating tumor DNA, and those did normalize even before they had their colonoscopy to examine their tumors.  So, again, we're continuing to see very encouraging data of immunotherapy, and the response rate with dostarlimab seems to be very interesting for this disease, and it will be interesting to see how this pans out in larger studies and how this translates into the use of dostarlimab across other diseases where other checkpoint inhibitors are currently being used. Geraldine Carroll: Absolutely. So, moving on to LBA3501. The COLLISION trial looked at surgery versus thermal ablation for small cell colorectal liver metastases. This was an international, multicenter, phase 3, randomized, controlled trial. How will this study change clinical practice?  Dr. Shaalan Beg: Kudos to the investigators here. They looked to understand the difference in outcome in treating people with colorectal cancer with liver only metastases. These clinical trials are extremely difficult to design. They're very difficult to enroll on because of the multidisciplinary aspect of the interventions and patient and provider biases as well. So on this clinical trial, the investigators enrolled people with resectable colorectal cancer, liver metastases so they did not have any metastases outside the liver. Patients were required to have 10 or less known metastases that were less than 3 cm in size. There were other allowances for larger tumors as well. And after an expert panel review, patients were randomized to either resection or ablation. It was up to the physicians whether they performed these laparoscopically or openly or percutaneously, depending on the biology of the patient and the anatomical presentation.  There was a predefined stopping rule at the half-time for this clinical trial, which showed a benefit in the experimental arm of ablation compared to standard of care. The overall survival was not compromised. Progression-free survival was not compromised with local therapy. But there were differences in morbidity and mortality, as we would expect, one being a surgical procedure and the other being ablation, where, according to this study, of the 140 or so patients who received either treatment, 2.1% of people who underwent resection died within 90 days of surgery. The AE rate was 56% in the resection sample compared to 19% in ablation, and the 90-day mortality for ablation was 0.7%. So less morbidity, improved mortality, reduced adverse events with ablation versus surgical resection without compromising local control and overall survival.   And I think for practice here in the United States, this does provide very interesting data for us to take back to the clinic for lesions that are relatively small and could generally be addressed by both surgery and ablation. Historically, there are various non biologic factors that could go into deciding whether someone should have surgery or ablation, and it could be based on who the physician is, who's seeing the patient, what the practice patterns in a specific organization are, and where their expertise lie. But here we're seeing that ablation for the small lesions is a very effective tool with very good local control rates, and again, in this selected group of patients with liver only metastases. And I think it is going to make tumor board discussions very interesting with data backing ablation for these lesions. Geraldine Carroll: Well, let's move onto the MOUNTAINER study. This study created some buzz in the colorectal cancer space. That's Abstract 3509. Can you tell us about the final results of this phase 2 study of tucatinib and trastuzumab in HER2-positive metastatic CRC? What are your thoughts on this treatment option, which seems to be well tolerated? Dr. Shaalan Beg: So, HER2 overexpression or amplification occurs in about 3 to 5% of patients with metastatic colorectal cancer and up to 10% of people who have a RAS/RAF wild type disease. On the previous episodes of the podcast we have covered precision targeted therapy in colorectal cancer, focusing on c-MET, focusing on BRAF, and here we have updated results targeting HER2 for colorectal cancer. And the results of the MOUNTAINEER study have been out for a while. This is a phase 2 study looking at combining tucatinib which is a highly selective HER2 directed TKI with trastuzumab, the monoclonal antibody for HER2 targeting. And what they found on this study is the confirmed overall response rate was 38%. Duration of response was 12 months, overall survival was 24 months and these are the results that have been already released and now we have an additional 16 months of follow up and these results continue to hold on. PFS and overall survival gains were held, which makes it a very interesting option for people with colorectal cancer. You mentioned the tolerability aspect and side effects. I think it's important to know the spectrum of side effects for this disease may be a little different than other TKIs. There's hypertension, but there's also the risk of diarrhea, back pain and pyrexia, with the most common grade 3 treatment related adverse event was an increase in AST level seen in 10% of people of grade 3 and above.  So where does that really leave us? There is a confirmatory randomized first-line trial of tucatinib and trastuzumab in the first line setting, which is currently ongoing. So we'll stay tuned to see where that leads us. And with the HER2 space right now for colorectal cancer with the development of antibody drug conjugates, we may have more than one option for this group of patients once those trials read out. Geraldine Carroll: Excellent. Well, moving on to LBA4008, that's the CheckMate-9DW trial. This trial reported first results looking at nivolumab plus ipilimumab versus sorafenib or lenvatinib as first-line treatment for advanced hepatocellular carcinoma. Can you tell us about this trial? Will there be a potential new standard of care in advanced HCC? Dr. Shaalan Beg: When we think about patients with advanced HCC, the only treatment option that they had for about a decade and a half were just oral track tyrosine kinase inhibitors that had modest to moderate clinical activity. Since then, we've seen that combination therapy is better than TKI therapy, and the combination therapy has taken two different forms. One is a combination of checkpoint inhibitor and antiangiogenic therapy, such as in the combination of atezolizumab and bevacizumab. The other is a combination of dual checkpoint inhibitor therapy. Here we are talking about the results of nivolumab and ipilimumab. Previously, we've talked about the combination of durva and tremi for the treatment of patients with HCC.   So in this study, nivo was given for the first 4 cycles, nivo and ipi were given together, nivo 1 mg per kg, and IPI 3 mgs per kg every 3 weeks for 4 cycles. And then the CTLA-4 inhibitor ipilimumab was stopped. And this was followed by monotherapy nivolumab every 4 weeks until disease progression or up to 2 years. And it was compared to dealers' choice, lenvatinib or sorafenib. The median overall survival of nivo-ipi was 23 months versus 20 months with lenvatinib-sorafenib. The 24-month overall survival was 49% with ipi-nivo versus 39%. And the overall response rate with nivo-ipi was 36% compared to 13%. So again, significantly improved clinical activity.   And when we talk about immunotherapy combinations, the question that comes to mind is how well is this tolerated? There's a lot of work and iteration that took place in figuring out what the right combination strategy of ipi and nivo should be, because some of the earlier studies did demonstrate fairly high adverse events in this group of patients. So on this study, we saw that grade 3 or 4 treatment related adverse events were seen in 41% of people who received nivo-ipi and 42% if they received lenvatinib or sorafenib. So, certainly a high proportion of treatment related adverse events, but probably also reflective of the disease population, which is being tested, because those numbers were fairly similar in the control arm as well.  So we've known that nivo-ipi is active in HCC. There is an approval in the second-line space, so it remains to be seen if this data helps propel nivo-ipi to the first-line space so we end up with another combination regimen for patients with advanced hepatocellular carcinoma.  Geraldine Carroll: Excellent. Well, before we wrap up the podcast, I'd like to ask you about LBA3511. In this study, investigators looked at total neoadjuvant treatment with long course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors. So this was a multicenter, randomized, open label, phase 3 trial. What are your key takeaways here? Dr. Shaalan Beg: Key takeaway here is that total neoadjuvant therapy was better than the conventional chemoradiation followed by chemo. So this clinical trial enrolled people with T4a/b resectable disease with clinical N2 stage, and they were randomized, as you mentioned, to receiving chemoradiation with radiation capecitabine followed by surgery, and then CAPOX or capecitabine versus chemo, short-course radiation, and additional chemotherapy followed by surgery.  And when we compare both arms, the total neoadjuvant therapy led to improved disease-free survival, improved PCR rates compared to standard concurrent neoadjuvant chemo radiotherapy in this group of patients. The two arms were fairly well-balanced. The number of T4 lesions was a little higher in the chemoradiation group. There were 49% in the chemo radiation group versus 46% had clinically T4 disease, but the nodal status was fairly similar. We should keep in mind that the other baseline characteristics were fairly well balanced.  And when we look at the outcomes, the disease-free survival probability at 36 months was 76% in the total neoadjuvant group compared to 67% with chemoradiation. And the metastasis free survival in total neoadjuvant therapy was 81% versus 73%. So a fairly compelling difference between the two arms, which did translate into an overall survival of 89% versus 88% in the two groups. So definitely higher disease-free survival and metastasis free survival, no difference on the overall survival with these groups. And it talks about the importance of intensifying chemotherapy upfront in this group of patients who can have a fairly high burden of disease and may struggle with receiving chemotherapy postoperatively. Geraldine Carroll: Excellent. Well, thank you, Dr. Beg, for sharing your fantastic insights with us on these key studies from the 2024 ASCO Annual Meeting. It's certainly a very exciting time in GI oncology. Dr. Shaalan Beg: Absolutely. Thank you for bringing these studies out, because I think a lot of these are practice-changing and can start impacting the clinical care that we're giving our patients right now. Geraldine Carroll: Thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: 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. 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.   Find out more about today's speakers: Dr. Shaalan Beg   @ShaalanBeg     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:  Dr. Shaalan Beg:   Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen   Speakers' Bureau: Sirtex   Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics   Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune  

In this episode of Meeting Mic, we bring you pearls and perspectives from the 2024 ASCO Annual Meeting, as well as Healio's top headlines from the meeting. Joseph A. Greer, PhD, discusses how early palliative care via telehealth had an equivalent impact on quality of life as in-person visits for patients with advanced non-small cell lung cancer. :27 Charu Aggarwal, MD, MPH, FASCO, further discusses these findings during a press briefing. 3:30 Heinz-Josef Lenz, MD, shares his thoughts on the first-line immunotherapy combination of nivolumab and ipilimumab in colorectal cancer. 4:35 Fumiko Chino, MD, discusses findings on the need for a more effective and transparent prior authorization process to ensure patients receive timely access to essential pain management. 7:09 Suneel Kamath, MD, provides an overview of findings assessing how the microbiome profile of early-onset pancreatic adenocarcinoma is distinct from that of average-onset disease. 10:22 Julie R. Gralow, MD, FACP, FASCO, discusses the important implications of a prospective study on young breast cancer survivors who attempted pregnancy and became pregnant. 12:54      Read the full coverage here: https://www.healio.com/news/hematology-oncology/20240602/we-have-the-technology-telehealth-increases-access-to-palliative-care-for-cancer https://www.healio.com/news/hematology-oncology/20240602/practicechanging-data-support-firstline-immunotherapy-combination-in-colorectal-cancer https://www.healio.com/news/hematology-oncology/20240531/findings-highlight-need-to-improve-prior-authorization-process-for-cancer-pain-management https://www.healio.com/news/hematology-oncology/20240603/tumor-microbiome-profiles-in-pancreatic-cancer-differ-by-age-of-onset https://www.healio.com/news/hematology-oncology/20220611/intramuscular-recombinant-erwinia-asparaginase-active-safe-in-leukemia-lymphoma-subsets Glucose-lowering drugs reduce risk for obesity-related cancers Source: Lin CH, et al. Abstract 10508. Presented at: ASCO Annual Meeting; May 30 – June 4, 2024; Chicago. Chemotherapy regimen improves survival in advanced esophageal cancer Source: Hoeppner J, et al. Abstract LBA1. Presented at: ASCO Annual Meeting; May 31-June 4, 2024: Chicago. Disclosures: Chino reports no relevant financial disclosures. Greer reports a consulting role with BeiGene; research funding from Blue Note Therapeutics and NCCN/AstraZeneca; and royalties from Oxford University Press and Springer Publishing Company. Please see the abstract for all other researchers' relevant financial disclosures.[JJ1]  Kamath reports no relevant financial disclosures.  Lenz reports honoraria from, consulting/advisory roles with, or travel, accommodations or expenses from 3T Biosciences, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Fulgent Genetics, G1 Therapeutics, GSK, Isofol Medical, Jazz Pharmaceuticals, Merck Serono, Oncocyte and Roche. Please see the abstract for all other researchers' relevant financial disclosures.

Dr. Shaalan Beg and Dr.Mohamed Salem discuss key abstracts that will be presented at the 2024 ASCO Annual Meeting, including hypoxia-response CAR T- cell therapy for solid tumors, GPC3-specific CAR T- cell therapy in hepatocellular carcinoma, and the promising efficacy of targeted therapies in GI cancers.  TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News Podcast. I am Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center. In today's episode, we'll be discussing some key abstracts in GI cancers that will be presented at the 2024 ASCO Annual Meeting. I'm delighted to welcome Dr. Mohammed Salem, a GI medical oncologist at the Levine Cancer Institute at Atrium Health, for this discussion. Our full disclosures are available in the transcript of this episode. Mohammed, it's great to have you back on the podcast. Dr. Mohamed Salem: Thank you, Dr. Beg. It's always a pleasure to be here. Thanks for having me.  Dr. Shaalan Beg: So we're seeing more and more exciting data emerge on the role of ctDNA in GI cancers. And that's a topic that we've covered fairly extensively on the podcast. This year, in Abstract 3513, investigators used a novel, highly sensitive HPV ctDNA assay to evaluate the clinical outcomes of HPV ctDNA status in people with localized anal cancer treated with chemoradiation. And we know that prior HPV infection is associated with 90% of anal cancers. Can you give us a summary of the study and why it's so important to the clinical care we're giving our patients today?  Dr. Mohamed Salem: Sure. So, as you already alluded to, in the current era of precision oncology or precision medicine in general, there is an effort to try to maximize treatment efficacy and minimize the side effects. We're trying to understand how to do that by developing more biomarkers. I think this was a very interesting study that was led by Dr. Morris of MD Anderson. As you mentioned, he tried to determine the correlation between that circulating tumor DNA at different timelines and also associated that with the relapse. Obviously, as we all know, HPV infection is linked to about over 90% of anal cancers, and anal cancer is increasingly common in the U.S.  The study design includes patients from stage 1, 2, and 3 anal cancer treated with curative intent concurrent chemo radiation and the plot sample to collect circulating DNA was taken at five weeks of treatment and then at various intervals, including 3months, 6  months, 9 months and 12 months, to detect the HPV circulating DNA. And the analysis was done to correlate detection of circulating DNA with a relapse.  So what they observed is after collecting the samples at the end of the treatment, which is 5 weeks, followed by 3 months, 6 months, 9 months, and 12 months following treatment using the correlation between the detection of circulating tumor DNA as well as the recurrence rate, they were able to identify that about 22% was seen at 5 weeks, 13% was seen at three months, then 10% was seen at 6 months, and 0% actually was seen at 12 months. In the final analysis, they concluded that detection of circulating DNA at 3 months was significantly associated with a relapse rate of those patients. And also, they looked at the baseline stage, T stage, end stage, age and other perhaps prognostic factors. But the clinical implication of that trial is this finding supports the potential of integrating now the circulating DNA analysis and routine post-treatment surveillance, which hopefully will help us identify those patients with high risk of relapse and whether they can be treated with adjuvant therapy  in context-free drug trial or even like more close surveillance. Obviously, this is a very novel study, so it needs validation. Also, we need to understand more about the platform used because with the immersion technology and how fast this field is moving, I think it's important to look at this platform or other platforms. I think as a concept it's very interesting and hopefully will help us to identify patients with higher risk. So, I'm looking forward to hearing the full presentation. Dr. Shaalan Beg: Moving on to colorectal cancer, Abstract 3514 is a trial of hypoxia-responsive CEA CAR T-cell therapy for people with heavily pretreated solid tumors where this was administered intraperitoneally or intravenously. And you know, as a solid tumor oncologist or GI oncologist, we've been watching the hematologic space evolve so dramatically in the last five years with cellular therapies that it's exciting to see these CAR T-cell approaches being applied in solid tumors with some results. So can you talk about this study and whether you think it will influence clinical practice?  Dr. Mohamed Salem: Of course, I'm actually very excited to see this study because as you mentioned, CAR T-cell therapy has been utilized in hematological malignancies for the last several years and in fact it's becoming a center of care. As you know, it's very effective in certain tumors. Unfortunately, we did not see a similar result in solid tumors thus far. I know we are trying to make progress, but we are definitely not seeing the same efficacy in solid tumors. And also, of course, in CRC and many other tumors, we need more target options, so I was very excited to see this abstract. And I want to give a little bit of background why this abstract is important. Many solid tumors have a low oxygen level environment, hypoxia obviously, which can impact the effectiveness of CAR T therapy. So hypoxia can suppress the immune response, leading to poor performance of the immune cells like the T cell within the tumor. The investigators, to overcome that challenge, meaning hypoxia impacting the efficacy of the T cell, they were actually able to engineer a CAR T cell to be hypoxia responsive. And what does that mean? That the cells are designed to become more active in low oxygen conditions, which is more difficult in many of the solid tumors. The reason that's very interesting is because, one, it reduces exhaustion of the T cell, meaning like when you have the T cell active all the time, they get exhausted. So when you have the T cell in the resting state, until they reach the tumor environment and they get activated by the hypoxia status, now you reduce the expulsion of the T cell. But also that one overcomes the resistance. So once activated in the tumor hypoxic environment, this CAR T cell shows increased efficacy in targeting and killing the cancer cell.  Based on that concept, the investigators conducted a phase 1 dose escalation study in solid tumors. So this was a phase 1 open label group escalation study involving patients with tumor suppressed CEA and also had relapsed refractory second line treatment. The trial actually included 2 routes of administration, which I think was very interesting – IV versus intraperitoneal, IP, way of administration. And they enrolled about 40 patients between June of 2022 and January 2023. And 35 patients had colorectal cancer, 3 patients had gastric cancer, and 2 patients had non-small cell lung cancer. Overall, there was no surprising safety data. In terms of side effects, it was largely macrocystis, colitis. Unfortunately, they had 1 treatment that did not finish. But the interesting feature was the efficacy of that concept was demonstrated and in fact they were able to see more disease response and control at this rate with IP infusion, which I think is a very novel approach. I would look forward to trying and looking into this kind of delivery, especially in CRC and other tumors. Dr. Shaalan Beg: Because we've known that historically managing disease intraperitoneally has been challenging with cytotoxic chemotherapies and even surgical approaches that have been deployed can be fairly morbid as well. So looking at novel delivery mechanisms can help us understand, maybe be able to manage side effects of treatments in different ways and open doors for treatment in diseases that otherwise we couldn't manage. So definitely a very novel and exciting approach on this study.  Dr. Mohamed Salem: I agree. I think the idea of administering an IP route is a very interesting idea.   Well, Shaalan, there is another study in CRC, Abstract 3515. This is the first human study of ABBV-400, cMET–targeting antibody-drug conjugate in advanced solid tumors. Can you tell us about this promising data? Dr. Shaalan Beg: Yeah, so we've known that cMET is a very relevant biomarker across many cancers, particularly colorectal cancer, and it is overexpressed in a fairly large proportion of multiple diseases. But there hasn't been an effective regimen that has been found to be tolerable to target this specific biomarker. In this study, the investigators are evaluating an antibody drug conjugate, which takes the cMET targeting antibody telisotuzumab and conjugates it to a novel topoisomerase one inhibitor payload. And there's a phase one study that enrolled people across multiple different tumor types. This was presented at ASCO 2023. And this year, the investigators are coming in and giving the results of a colorectal cancer cohort within that study. Patients were enrolled in the dose escalation phase, and in the dose expansion phase, there were 122 colorectal cancer cases; so a fairly healthy size colorectal cancer population. And the median number of prior lines of therapy was 4, which is fairly consistent with what we would expect in our clinical population for people with colorectal cancer. So what they found in terms of efficacy is that the response rates, the confirmed overall response rates, were between 15 and 20%, depending on what dose of the medication the patients had received. They enrolled people regardless of cMET expression and then evaluated the response based on a higher or lower cMET expression. And those with higher cMET expression had an overall response rate of >30%, while those with lower cMET expression had a response rate of 10 to 15%. So they still had a response rate, which for fifth-line colorectal cancer is something to be aware of and it could be a marker of more significant clinical activity than other treatments that are out there.  And with the antibody drug conjugates, it's also important for us to keep an eye on the side effect profiles because a lot of these agents can have distinct side effect profiles that otherwise we wouldn't be familiar with. And in this study, 64% of participants had a grade 3 or above treatment emergent adverse events, and 41% had serious adverse events. So definitely something to think about. And most of these were hematologic toxicities, 30% had grade 3 or worse anemia. Neutropenia was seen, in grade three and above, was seen in 25%, leukopenia or grade three and above was seen in 12%, and thrombocytopenia again around 12%. And the non-hematologic toxicities were nausea, fatigue, vomiting and diarrhea. There was some interstitial lung disease, pneumonitis, which was seen in 7% of the total population, of which 2% had grade three or above. So definitely something to think about. From my perspective, I really am excited about this presentation because we're seeing evidence of clinical activity focused on cMET for refractory colorectal cancer compared to other agents that are out in the market. If this pans out in future studies, it could definitely change the way we deliver our treatments. Dr. Mohamed Salem: I totally agree that we actually need more therapy for those patients. And I'm not surprised that the myelosuppression, as you mentioned, was in fifth-line treatment. So this patient had large exposure to cytotoxic agents before.   So, looking at CAR T once more, there is a very interesting Abstract 4019, which is a study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR T, in patients with advanced hepatocellular carcinoma (HCC). What are your key takeaways from this study, Shaalan? Dr. Shaalan Beg: This is a first-in-human study. It enrolled people with advanced HCC who failed on one or more lines of prior therapy and they were given one single infusion of C-CAR031 after standard lymphodepletion and they enrolled 24 patients across 4 dose levels. If we look at the overall response rate, 50% of the 22 people who were eligible for response assessments had a partial response. This response rate varies based on the dose level itself and the investigators claim a 90% disease control rate. So definitely when we think about standard treatments for hepatocellular cancer after first line therapy, this is something which will catch a lot of people's attention. Again, with CAR T-cell therapy, we need to be aware of the risk of potential toxicities. There were no dose limiting toxicities and CRS or cytokine release syndrome was observed in 91% of patients, while a very small proportion, about less than 5%, had grade three CRS. Most of the side effects here were, again, lymphocytopenia, neutropenia, thrombocytopenia, and some transaminitis in 16% of patients. They did see tumor reduction in 90%, not only in the intrahepatic disease, but also in the extrahepatic disease. And again, these are people who had BCLC stage C disease. So this included people with hepatic and extrahepatic metastases. And in terms of prior lines of therapy, 96% of patients had either received immune checkpoint inhibitors and TKIs.  If we think about how some other immune therapy regimens are being developed in the GI cancer space, there is some indication that liver lesions may respond differently compared to extra hepatic disease. So in this case, they saw responses in both scenarios, which makes it very exciting, because even though we've seen many approvals of TKIs and immunotherapy, anti-androgenic therapy in hepatocellular cancer, the treatment of these patients is still extremely difficult because of their underlying hepatic dysfunction. And it'll be very interesting to see how this treatment unfolds.  Dr. Mohamed Salem: You summarized it very well, Shaalan. I echo your thoughts. What is also interesting about that study, it's actually targeted at the GPC strain, which is prevalent in HCC but not normal tissue, which goes back to your comment about the toxicity, and hopefully we can also manage treatment in the context of underlying liver disease.  Dr. Shaalan Beg: I guess it's fair to say that we're both very excited to see what's ahead in GI cancers at the Annual Meeting.   Mohamed, thanks as always for sharing your great insights with us on the ASCO Daily News Podcast.  Dr. Mohamed Salem: Thank you all for having me, and I'm looking forward to meeting you and all our colleagues in Chicago in a couple of weeks. Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcripts of this episode. I'll be back to cover late breaking abstracts and other key advances in GI oncology after the annual meeting, so please join me for more key insights from ASCO24 and on the ASCO Daily News Podcast. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: 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.   Find out more about today's speakers:  Dr. Shaalan Beg  @ShaalanBeg  Dr. Mohamed Salem  @SalemGIOncDoc    Follow ASCO on social media:  @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Shaalan Beg:  Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen  Speakers' Bureau: Sirtex  Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics  Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune    Dr. Mohamed Salem: Consulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol-Myers Squibb, Exelixis, QED Therapeutics, Novartis, Pfizer, Daiichi Sankyo/Astra Zeneca  Speakers' Bureau: Genentech/Roche, Taiho Pharmaceutical, Daiichi Sankyo/Astra Zeneca, BMS, Merck 

Für den Wirtschaftsstandort Genf war es eine Hiobsbotschaft: am 24. April 2012 kündigte der deutsche Pharma- und Chemiekonzern Merck an, den Hauptsitz seines Ablegers «Merck Serono» in Genf zu schliessen und hunderte Stellen abzubauen. Die Angestellten und die Politik reagierten schockiert.

Drs. Shaalan Beg and Aparna Parikh discuss the role of ctDNA as a powerful prognostic biomarker for GI cancers, along with its impact on risk stratification and the detection of recurrence. They highlight key studies in ctDNA that were featured at the 2024 ASCO GI Cancers Symposium, including COBRA, GALAXY, and BESPOKE in CRC, as well as the promise of ctDNA testing in the preoperative detection of iCCA. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Shaalan Beg, your guest host for the ASCO Daily News Podcast today. I am an adjunct associate professor at UT Southwestern's Harold Simmons Comprehensive Cancer Center in Dallas. On today's episode, we will be discussing the emergence of circulating tumor DNA (ctDNA) technology in GI cancers. I am delighted to be joined by Dr. Aparna Parikh, an assistant professor of medicine at Harvard University and the director for colorectal medical oncology at the Massachusetts General Hospital Cancer Center, where she also serves as the medical director of the Young Adult Colorectal Cancer Center. Dr. Parikh will share her insights on key research on this hot topic in GI oncology that was featured at the recent ASCO Gastrointestinal Cancers Symposium.  Our full disclosures are available in the transcripts of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Parikh, it's great to have you on the podcast today. Dr. Aparna Parikh: Thanks so much, Dr. Beg.  Dr. Shaalan Beg: In recent years, it has become evident that liquid biopsy and other emerging ctDNA technologies are changing how we treat GI cancers, and colorectal cancer (CRC) is in the forefront of this space. Before we dive into key studies, can you briefly highlight for our listeners how ctDNA is advancing the field and how it can influence the care that we deliver to our patients in the future? Dr. Aparna Parikh: Absolutely, ctDNA is certainly a hot topic. What we have learned over the years is that ctDNA has emerged across many solid tumor types as one of the most powerful, if not the most powerful, prognostic biomarker we have to date. ctDNA has improved risk stratification. We have learned a lot about the role in what is called minimal or molecular residual disease in patients with early-stage disease, and ctDNA being a biomarker of recurrence for those patients, with ctDNA, we have a better understanding of tumoral heterogeneity, both spatially and temporally, getting a better glimpse of what is happening in a given patient with multiple metastases, as well as genomic evolution of tumors over time. So certainly many, many roles and areas where ctDNA is emerging. Dr. Shaalan Beg: This was a hot topic at the 2024 ASCO GI Cancers Symposium, and we're going to take a deep dive into some of the abstracts that were presented. Let's start with the COBRA study, which is the NRG-GI005. That was Abstract 5 at the ASCO GI Cancers Symposium, and the GALAXY study, which was Abstract 6 at the symposium. So, the COBRA study reported results of ctDNA as a predictive biomarker in adjuvant chemotherapy for people with colon cancer. At a high level, it was a negative study, but there are some important lessons for us to learn. Similarly, in the GALAXY study, investigators from Japan presented an updated analysis on the correlation of ctDNA dynamics with outcomes in colorectal cancer with minimal residual disease. How do you synthesize all this information and help the listeners understand our current state for ctDNA applications in colorectal cancer? Dr. Aparna Parikh: Yeah. Let's take the COBRA study first. Let's talk a little bit about the design of COBRA. COBRA was intended to look at patients that were resected, stage 2 colorectal cancer patients, or colon cancer patients who were 2A. These are patients where the treating physician would, at the outset, decide that there was no adjuvant chemotherapy indicated. These are patients where active surveillance would be entirely appropriate as the standard of care. Patients were randomized to arm 1, which was active surveillance, or randomized to arm 2, which was assay-directed therapy. If there were ctDNA positive in arm 2, then they were given chemotherapy, FOLFOX or CAPOX. And if they were “ctDNA not detected,” then they would also go on to active surveillance.   And so, the plan was that nearly 1,500 patients are to be recruited, and at the time of this data cut, they had around 630-some patients. The primary objective was to look at the clearance rates of ctDNA between the ctDNA-positive cohorts, remember, the chemotherapy and the active surveillance cohorts at 6 months. They had around a 5% detection rate of ctDNA patients. Ultimately, that was around 16 patients. The reason that the study shut down was that what they found was that in the surveillance arm, the arm that was not getting any treatment, they had a ctDNA clearance of 43% versus 11% in the chemotherapy arm. They had an interim analysis to look at the clearance rate between the 2 arms, and what was surprising to the investigators and the community was what was happening in terms of clearance. Why do we have a 43% clearance rate in patients that were not getting anything? And so, because of that, the study was shut down as it did not meet its prespecified interim look at clearance in those 2 arms.   Many things came up in terms of learnings from COBRA. Number one was the characteristics of the assay. And so, you take an assay in a low-risk patient population that has a fixed specificity, and when your baseline prevalence of recurrence is so low, for example, in low-risk stage 2 patients, your composite predictive value is very susceptible to small changes in that specificity. And so, your PPV is going to be a lot lower in a low-risk patient population than a higher-risk patient population. The COBRA study used an older version of a tumor-uninformed assay, so it definitely called into question some characteristics of the assay. Is one-time-point clearance sufficient, and is that the right endpoint? We have seen now, including the GALAXY study that we'll talk about here, previously reported just spontaneous clearance happening in 5%, 10% of patients. The question with that spontaneous clearance is: Was it actually clearance, or was chemotherapy just perhaps in a low ctDNA shedding state? Are you just suppressing the ctDNA below the level of limited detection?  And then in this study, the clearance draw was actually done in the chemotherapy arm right before the last cycle of chemotherapy, again to that point of, are you just suppressing the ctDNA with chemotherapy? There is also stochastic sampling error that can happen in patients with very low residual tumor volume. So, I think this is a disappointing study in the sense that it is still a really important question. There are still 2A patients that recur, but maybe [this was] not the right test, or maybe single-time-point testing wasn't enough. And so, lots of lessons to be learned from this study in terms of test and design, but hopefully more to come. I think certainly stage 2 patients remain an area where I think, hopefully, ctDNA still plays a factor for those patients.  Dr. Shaalan Beg: And how was the patient population for the GALAXY study? That was Abstract 6, compared to the COBRA study. Could you summarize those findings for us?  Dr. Aparna Parikh: Yeah, so GALAXY was part of a large study in Japan that includes an observational cohort plus therapeutic cohorts as well. And so, GALAXY was just further reporting of the observational cohort. So unlike COBRA, which is a low-risk, stage 2 study that was actually asking that interventional question: Can you use it to guide therapy? The GALAXY and the updated GALAXY just continues to show more clinical validity data rather than clinical utility data. And it was nearly 3,000 patients, pan stages. Again, the lion's share were stage 2 and 3 patients, but there were also stage 1 and stage 4 patients as well. And what they showed was that ctDNA is undoubtedly prognostic. They showed very consistent Kaplan-Meier curves, which we've seen time and time again, where if you're ctDNA-positive, you don't do as well.  What they showed was, not surprisingly, with longer-term follow-up – this is 24-month follow up, so longer-term follow up than was published in their paper last year – was that when you test at one time point, so landmark testing, the sensitivity of detecting recurrence was around 48%, and that fell from the publication last year which was around 58%, 59%, which is not surprising as you follow more people. I think single time point testing soon after surgery may miss those late recurrences, but it's still prognostic and showed a specificity of around 94%.   They also continued to show that if you continued to test with serial testing, your sensitivity improves, but what was really interesting and new, what they presented this time, was a clearance analysis. And showing, again, comparable to COBRA, in many ways, in the sense that clearance can be a little bit finicky, especially at one time point, is what they showed is that patients who had sustained clearance, and these are patients that had at least two time points with their ctDNA remained to be negative, they did very well. But if you had transient clearance, and again, the definition was a little bit broad, at least having one negative and then one positive, those patients ultimately, at 24 months, the curves came together with the no clearance curve. So initially, they did better than the people that didn't have any clearance. But if you transiently cleared at two years, the curves came back together.   And what was interesting is that in those patients that sort of transiently clear by 9 to 12 months, 80% of those are actually having a rapid return of ctDNA. And so this begs the question of was chemotherapy just suppressing that ctDNA or maybe if you have a better test you could have actually improved it.  These were some of the updated, interesting learnings from GALAXY, which remains incredibly prognostic. And then the concept of clearance, which I think we have to look into a little bit more as a field, and understanding that maybe just one time point clearance isn't sufficient.  Dr. Shaalan Beg: Yeah, and one of the most important applications for ctDNA can be its ability to inform adjuvant chemotherapy. Its ability to not only identify more people who may benefit from chemotherapy, but maybe even identify people who don't need chemotherapy. And along those lines, Abstract 9, the BESPOKE study, looked to understand the role of ctDNA-based detection of molecular residual disease to inform adjuvant therapy for stage 2 and 3 colorectal cancer. And they presented interim data at the GI ASCO this year. What were your takeaways from this study? Dr. Aparna Parikh: Exactly. Beyond the prognostic implications, I think what was really interesting was that there was the initial data looking at the benefit of adjuvant chemotherapy. So, what they did was they said, “Okay. We're going to take the MRD-positive patients and look at the benefit of adjuvant chemotherapy and then the benefit of adjuvant chemotherapy in the MRD-negative patients.” And again, remember, this is a prospective observational study, so it's not looking at negative and positive to guide therapy, but it's just looking prospectively and observationally at how those patients are doing. But what they showed again is that indeed, in the adjuvant chemotherapy group, the benefit of adjuvant chemotherapy again with the follow-up to date on the study was different in the MRD-positive patients.  First of all, I guess taking a step back, the DFS in the ctDNA-negative patients at 2 years was very good. So negative patients had over 98% 2-year DFS in both the adjuvant chemotherapy and observational group. And there was no real difference between adjuvant or not. But in the positive patients, not surprisingly, the DFS was worse. But what was reassuring to see is that you can make an impact with adjuvant chemotherapy in the positive patients. And the difference in DFS between the positive and negative patients, with adjuvant or not, was 42% versus 12.5%, in the observational patients. So, it is benefitting the patients who are positive so it does give us more data that, again, at least in the positive patients, you may be able to reverse the recurrences there with adjuvant chemotherapy. And maybe if you're negative, eventually, we'll get to a point of de-escalation of care. Again, keeping in mind the kinds of sensitivity limitations as well.  Dr. Shaalan Beg: Wonderful. And one of the other malignancies in the GI space where precision therapies and molecular biomarkers are making a huge difference are intrahepatic cholangiocarcinoma. Genomic profiling using ctDNA is increasingly being used in this population to inform precision oncology approaches and determine mechanisms of resistance to targeted therapies as well. In Abstract 528, investigators looked at the role of preoperative ctDNA testing for resectable intrahepatic cholangiocarcinoma. What are your thoughts on that study?  Dr. Aparna Parikh: Yeah, it's such an important area, as you mentioned, in the metastatic space – FGFR, IDH1, all these alterations that are emerging in intrahepatic cholangios. This was a very small study, it was preoperative, and so the tumor was intact, and around 14 patients. They used a tumor-informed approach just for detection and quantification of ctDNA. So this was not a study that was looking at a next-generation sequencing approach where you're going to actually be able to detect the alterations, but it's actually looking for the detection and quantification of ctDNA rather than genomic characterizations. And patients had about a month or so where they had their baseline blood detected. And I think what was reassuring to say was that ctDNA was actually detected in all the patients with the primary tumor intact, except for one patient who was a very low-risk stage 1A patient. There was some correlation, against a small number of patients, between the concentration of ctDNA in patients that had the lower stage and then the higher stage groups. Small numbers were actually hard to characterize and correlate with recurrence or mortality, but at least, some correlation with pathologic tumor size, they were able to because it was a bespoke panel and you're sampling the tissue and then looking in the blood, IDH1 and 2 were mutations that were tracked based on the genomic profiling and a couple of the patients were able to have their IDH mutations tracked.  So it gives us a sense, a little bit, that ctDNA, we know has a lot of variable shedding across disease states and tumor locations, but gives us some promise that it is reliably detected with the tumor-informed approach, at least preoperatively in cholangios. So may again open some more opportunities for MRD testing in cholangiocarcinoma as well.  Dr. Shaalan Beg: Thank you. That's a wonderful review of ctDNA applications in gastrointestinal cancers from the 2024 ASCO GI Cancers Symposium. Thank you, Dr. Parikh, for sharing your valuable insights with us on the podcast today. Dr. Aparna Parikh: Thank you so much for having me. Dr. Shaalan Beg: Thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: 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.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Aparna Parikh @aparna1024   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Aparna Parikh: Consulting or Advisory Role (An Immediate Family Member): PMV Consulting or Advisory Role: Checkmate Pharmaceuticals, Guardant Health, Foundation Medicine, Abbvie, Value Analytics Labs, Bayer, Taiho Oncology, Delcath, Seagen, CVS, SAGA Diagnostics, Scarce, Illumina, UpToDate, Takeda, AstraZeneca, Takeda, Pfizer, Kahr, Xilio Therapeutics, Sirtex Research Funding: PMV Pharma, Erasca, Inc, Syndax Research Funding (Institution): Bristol-Myers Squibb, Genentech, Guardant Health, Array, Eli Lilly, Novartis Pharmaceuticals UK Ltd., PureTech, Mirati Therapeutics, Daiichi Sankyo, Karkinos Other Relationship: C2i Genomics, Xgenomes, Parithera, Cadex

Drs. Shaalan Beg and Travis Osterman discuss a machine learning model, recently featured in JCO Clinical Cancer Informatics, that uses electronic health record data to accurately predict the effectiveness and toxicity of treatment with immune checkpoint inhibitors. The new AI model can be used to provide a personalized risk-benefit profile, inform therapeutic decision-making, and improve clinical trial cohort selection.   TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host for today. I am an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center.  Cancer immunotherapy has transformed the treatment landscape by providing new and effective treatment options for many solid and hematologic malignancies. But while many patients experience a remarkable response to immune checkpoint inhibitors, other patients can suffer life-threatening immune checkpoint toxicities. Today, we will be discussing a machine learning solution that can assess a patient's immune checkpoint inhibitor risk-benefit profile based primarily on routinely collected structured electronic health record data. This novel AI solution was recently featured in JCO Clinical Cancer Informatics, and I am delighted to welcome one of the report's authors, Dr. Travis Osterman. He is an associate vice president for research informatics and associate professor in the Department of Biomedical Informatics and the Division of Hematology Oncology at Vanderbilt University Medical Center in Nashville, Tennessee. Dr. Osterman also serves as the director of cancer clinical informatics at the Vanderbilt Ingram Cancer Center.  Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Osterman, it's great to have you on the podcast today.   Dr. Travis Osterman: Thanks, Shaalan. It's great to be here. Thank you for the invitation.   Dr. Shaalan Beg: Congratulations on your recently published article in the JCO CCI titled "Prediction of Effectiveness and Toxicities of Immune Checkpoint Inhibitors Using Real World Patient Data." Why did you decide to address this specific problem?   Dr. Travis Osterman: I am a practicing medical oncologist at Vanderbilt, I specialize in thoracic malignancies. Immunotherapy has been a significant part of my practice from the beginning. And I think for all of us, we have patients in our practices that are tremendous responders. I have stories of my patients, a few of which, at least, are able to get years of benefit even after stopping therapy, and potentially some even stage 4 patients that are amazingly seemingly cured after their treatments. But I also have patients that experience severe toxicities, some of those are life-threatening or life ending, but many of those carry morbidity. In my population, I see a lot of pneumonitis, and that really alters patients' quality of life. And the biggest conversation I have with patients is: “How do I know which of these outcomes I'm going to have, if I'm going to get benefits from these therapies or am I going to get one of these side effects or toxicities?” And we set out to try to answer that question with data.   Dr. Shaalan Beg: When electronic medical records started to make their way into the clinic, I remember all of us thinking about the wonderful applications where we could use the data to help guide the clinical care, assign the right treatment for the right patient at the right time, and learn from other patients' experiences to improve the care of the person who's in front of us. And my personal opinion is that we haven't realized our electronic medical records' potential to that extent. And efforts like the one you published in JCO CCI is the culmination of one of the efforts, and I can only imagine how much time and effort it must have taken to develop that and we're hoping is the first of many more to come. For our listeners, can you talk us through the steps required to develop such a tool, and why now is the right time, and why we're starting to see these evolve?   Dr. Travis Osterman: This project would not have been possible 20 years ago. It relies on having what we would call structured data available for our patients that are receiving cancer care, so that's vital signs, laboratory values, and diagnoses, all of the things that we routinely collect in the electronic health record. So that is step 1. This project required that those systems be not just in place at academic centers but be widely available because our goal is to set up systems that will be able to transform cancer care, not just at academic institutions, but for the entire practice of oncology.  The second piece is you need enough data to be able to train these models. And so, we needed to be practicing with checkpoint inhibitors long enough to see patients that had toxicities, to see patients that had benefit, and then to jump into the data science of actually trying to learn from them. And so this really was the culmination of systems put in place by a lot of people before us and then really the right time [when] we started to have now enough data to really start to learn from.   Dr. Shaalan Beg: The publication discusses the steps of how you validated your tool. Talk me through how you see this being applied to the point of care for the next time you are about to start an immune checkpoint inhibitor for your lung cancer patient?   Dr. Travis Osterman: I think there are two different primary lanes that these types of models can be applied. In the drug development space, I think many of us are familiar that many assets, many drugs that are in the development pipeline are halted because of adverse events in toxicity profiles, but we also realize that not everyone gets those toxicities. And so we envision a future where before a drug that's in the drug development pipeline is taken out of the development pipeline, potentially, you could screen patients that are at lowest risks of actually having side effects from that immunotherapy and only screen those patients into the trial and that would potentially make more drugs available to more patients going forward. So I think that that's 1 lane.  I think the other lane in clinical practice is, let's say that I'm treating a patient who we determine has an increased risk for colitis. Instead of only seeing that patient back in 3 weeks, potentially, now, what if I had one of our nurse navigators, call the patient at weekly check-ins between visits to check in and see whether or not they were having any episodes of diarrhea and trying to intervene earlier. That might allow us to keep patients both out of the hospital, out of the emergency department to treat their symptoms more quickly to decrease the severity of their toxicity and keep them on treatments, especially if they're receiving benefit from it. So, I think there's an opportunity to improve both drug development and making more drugs available to patients and then also to identify patients that are at risk for toxicity, and then to do interventions to help mitigate those risks. Really, the idea of precision risk mitigation.   Dr. Shaalan Beg: One of the problems with electronic medical record-based tools in the past has been that they don't evolve with time. We develop it, we set it, we deploy it, and it almost feels, to the users at least, that it stops evolving after that. With novel therapeutic agents coming into the clinic, we're seeing new ADCs, new novel checkpoint inhibitors entering the market. How do you envision tools such as yours to be refreshed so they can stay relevant with the modern armamentarium of medications which are being used?   Dr. Travis Osterman: So, if you ask any data scientist, the most requested item they will ask for is more data. And so, this initial set of models that we've described in this publication were trained exclusively on a single institution's data at Vanderbilt University Medical Center as we continue both to see more patients here, and then ideally look forward to collaborations with other centers. We expect that these models will continue to be refined and that the performance will improve as we increase the amount of training data, and we hope that that will do 2 things. One, it will counteract the kind of model drift that you described. But then two, it will allow us to ask some more specific questions that honestly, we weren't really powered to answer in our study here. For instance, we didn't look at cardiac toxicity, which is a concern if you're giving a CTLA-4 along with a PD-1 or PD-L1 inhibitor more so than single agent immunotherapy. We just don't have enough events to be able to train models on that. But with future collaborations, that would be a question we would love to tackle as well.  One of the things that's interesting about the implementation of these models is that we found many of the features that I would have expected to find as a practicing oncologist. For instance, when we're trying to predict the toxicity of pneumonitis inflammation of the lung, I as an oncologist would think that many of my patients that have COPD or interstitial lung disease at baseline seem to be at a higher risk. And so that's one of the features that I was looking to come out in the model. And that's exactly what we found. That was one of the contributing features that helps us predict a higher risk of pneumonitis. But what's interesting is that's certainly not the only feature; there end up being about a dozen features that are in that space that help predict that toxicity.   Similarly, for colitis, we found that the combination of receiving a CTLA-4 inhibitor in addition to a PD-1 or PD-L1 inhibitor, that combination together, which would increase risk for colitis, which is well-documented in our literature. So these models are not entirely black boxes. We've published the top features of these models that contribute to our predictions. And I think clinically the challenge for me has always been if I have a patient who has COPD, but it's pretty well-controlled and their O2 sat is normal, how does that patient's risk bring pneumonitis compared to someone who has poorly controlled COPD with low O2 sat at baseline, etc.? And so these models are really designed to help tease out some of those nuances.   Dr. Shaalan Beg: There are so many wonderful applications to use preexisting data that can improve the lives of our patients and frankly that can improve the work experience for clinicians. They can be used for risk stratification using these preexisting data. Can you talk a little bit about what are the barriers that people face or that your team faced in developing these tools, and what has changed or what's expected to change in the coming years to allow people to continue developing tools such as what was described?   Dr. Travis Osterman: I think it's important to realize that we are not unique in addressing this problem. This is a problem that I think has been a focal point of our cancer informatics community for the better part of the last, probably, decade. I think one of the things that distinguishes the work that we've done here is really this idea of clinical utility. And what I mean is we focused on data that would be collected at any routine oncology visit in the U.S., and I would argue worldwide, to use as features in our model. So, we're not running complex genetic testing that may or may not be paid for. We're not asking for new laboratory values to be sent or for extensive questionnaires that aren't already in clinical practice. We're using pieces that are already being connected into the pipeline of oncology practices, and I think that's one of the differentiators of this project versus many others in this space.  Right now, these are only EHR data. We have a part of our project that's looking at imaging data and whether that adds value. But one of the pieces that I always advocate for, if we're going to ask practices for instance to upload these imaging files or to send a CD to a central location to improve the outcome, that's harder to work into an oncologist workflow than if all the data are already there in the health record and you can click a button and calculate this person's risk profile. And so, we've really tried to be pragmatic about our approach as we've entered this realm and that's been a real focus of our team.   Dr. Shaalan Beg: Many of the listeners of today's podcast are busy clinicians, and you talked about how the idea for this project came from the problem you witnessed in your clinic. How can clinicians continue to be involved in such initiatives or drive these initiatives at their own institutions, in office situations where they may not have the resources that your team has? Can you speak to national efforts or collaborations in this regard?   Dr. Travis Osterman: Yeah. So, first of all, I would invite really anyone to reach out to our team, if they're in a position where they'll be interested in validating our models at their local institutions. We would be happy to work with them to provide the models to see how they perform on their data sets. I think that that's an important part of the academic review and informatics is to see how these models translate into other health care settings. And we also are interested to make sure that what I said in the prior discussion is correct, that we're only incorporating things that other institutions already have. So I think that that's certainly one.  The second is a part of a large National Cancer Data standard project called mCODE, the Minimal Common Oncology Data Elements, I chair that executive committee. And one of the pieces of that is trying to find a way to make all of these kinds of structured data interoperable between health records. And so I would just encourage all of my colleagues to always advocate for interoperability and, when there's an option, to store data in a way that makes that data more easily shared in the same formats between institutions. I think that that will pay many dividends for our field going forward. And I just want to plug all the team at mCODE for their work in this and maybe there'll be an integration and connection between mCODE and our project in the future.   Dr. Shaalan Beg: Thank you very much Dr. Osterman for sharing your insights with us today on the ASCO Daily News Podcast.   Dr. Travis Osterman: Thanks, Shaalan. Have a great day.   Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find a link to Dr. Osterman's article in the transcript of this episode. And if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   Disclaimer: 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.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Travis Osterman @TravisOsterman   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Travis Osterman: Stock and Other Ownership Interests: Faculty Coaching Honoraria: Amazon Web Services Consulting or Advisory Role: eHealth, AstraZeneca, Outcomes Insights, Biodesix, MD Outlook, GenomOncology, Cota Healthcare, Flagship Biosciences, Microsoft, Dedham Group, Oncollege Research Funding: GE Healthcare, Microsoft, IBM Watson Health Travel, Accommodations, Expenses: GE Healthcare, Amazon Web Services

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RGD865. CME/AAPA credit will be available until February 28, 2025.Leveraging TROP2 Expression in NSCLC: Expert Perspectives on the Present Evidence and Future Potential of TROP2-Targeting ADCs in Lung Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerCharu Aggarwal, MD, MPH, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; BeiGene; Blueprint Genetics; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo/AstraZeneca; Eisai; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck and Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./Sanofi; Shionogi Inc.; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; Macrogenics, Inc; and Merck Sharpe and Dohme LLC.Faculty/PlannerProf. Solange Peters, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; Arcus Biosciences; AstraZeneca; Bayer AG; BeiGene; BerGenBio; Biocartis; BioInvent; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; Daiichi Sankyo Co., Ltd.; Debiopharm International SA; ecancer; Elsevier; F. Hoffmann-La Roche/Genentech; F-star Therapeutics Inc.; Fishawack Health Group; Foundation Medicine, Inc.; Genzyme; Gilead Sciences Inc.; GlaxoSmithKline: HUTCHMED; Illumina, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; IQVIA Inc.; iTeos Therapeutics; Janssen Global Services, LLC; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Merrimack; Mirati Therapeutics, Ind.; Novartis; Novocure; Pfizer; PharmaMar AG; Promontory Therapeutics; Regeneron Pharmaceuticals Inc.; Sanofi; Seattle Genetics; Takeda Pharmaceutical Company Limited; and Vaccibody. All fees to institution.Grant/Research Support from (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen Inc.; AstraZeneca; Biodesix, Inc.; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; F. Hoffmann-La Roche/Genentech; GlaxoSmithKline; Illumina, Inc.; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Mirati Therapeutics, Inc.; Novartis; Pfizer; and Phosplatin Therapeutics.Other Financial or Material Support for talks in a company's organized public event from AstraZeneca; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; ecancer; F. Hoffmann-La Roche/Genentech; Illumina, Inc.; Lilly; Merck Sharp and Dohme Corp.; Novartis; Pfizer; Sanofi; and Takeda Pharmaceutical Company Limited. All fees to institution. On the Board of Directors for Galencia SA.Faculty/PlannerJacob Sands, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Boehringer Ingelheim; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; Lilly; Medtronic; PharmaMar, and Sanofi.Grant/Research Support from Amgen Inc. and Harpoon Therapeutics.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RGD865. CME/AAPA credit will be available until February 28, 2025.Leveraging TROP2 Expression in NSCLC: Expert Perspectives on the Present Evidence and Future Potential of TROP2-Targeting ADCs in Lung Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerCharu Aggarwal, MD, MPH, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; BeiGene; Blueprint Genetics; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo/AstraZeneca; Eisai; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck and Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./Sanofi; Shionogi Inc.; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; Macrogenics, Inc; and Merck Sharpe and Dohme LLC.Faculty/PlannerProf. Solange Peters, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; Arcus Biosciences; AstraZeneca; Bayer AG; BeiGene; BerGenBio; Biocartis; BioInvent; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; Daiichi Sankyo Co., Ltd.; Debiopharm International SA; ecancer; Elsevier; F. Hoffmann-La Roche/Genentech; F-star Therapeutics Inc.; Fishawack Health Group; Foundation Medicine, Inc.; Genzyme; Gilead Sciences Inc.; GlaxoSmithKline: HUTCHMED; Illumina, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; IQVIA Inc.; iTeos Therapeutics; Janssen Global Services, LLC; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Merrimack; Mirati Therapeutics, Ind.; Novartis; Novocure; Pfizer; PharmaMar AG; Promontory Therapeutics; Regeneron Pharmaceuticals Inc.; Sanofi; Seattle Genetics; Takeda Pharmaceutical Company Limited; and Vaccibody. All fees to institution.Grant/Research Support from (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen Inc.; AstraZeneca; Biodesix, Inc.; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; F. Hoffmann-La Roche/Genentech; GlaxoSmithKline; Illumina, Inc.; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Mirati Therapeutics, Inc.; Novartis; Pfizer; and Phosplatin Therapeutics.Other Financial or Material Support for talks in a company's organized public event from AstraZeneca; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; ecancer; F. Hoffmann-La Roche/Genentech; Illumina, Inc.; Lilly; Merck Sharp and Dohme Corp.; Novartis; Pfizer; Sanofi; and Takeda Pharmaceutical Company Limited. All fees to institution. On the Board of Directors for Galencia SA.Faculty/PlannerJacob Sands, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Boehringer Ingelheim; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; Lilly; Medtronic; PharmaMar, and Sanofi.Grant/Research Support from Amgen Inc. and Harpoon Therapeutics.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RGD865. CME/AAPA credit will be available until February 28, 2025.Leveraging TROP2 Expression in NSCLC: Expert Perspectives on the Present Evidence and Future Potential of TROP2-Targeting ADCs in Lung Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerCharu Aggarwal, MD, MPH, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; BeiGene; Blueprint Genetics; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo/AstraZeneca; Eisai; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck and Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./Sanofi; Shionogi Inc.; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; Macrogenics, Inc; and Merck Sharpe and Dohme LLC.Faculty/PlannerProf. Solange Peters, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; Arcus Biosciences; AstraZeneca; Bayer AG; BeiGene; BerGenBio; Biocartis; BioInvent; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; Daiichi Sankyo Co., Ltd.; Debiopharm International SA; ecancer; Elsevier; F. Hoffmann-La Roche/Genentech; F-star Therapeutics Inc.; Fishawack Health Group; Foundation Medicine, Inc.; Genzyme; Gilead Sciences Inc.; GlaxoSmithKline: HUTCHMED; Illumina, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; IQVIA Inc.; iTeos Therapeutics; Janssen Global Services, LLC; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Merrimack; Mirati Therapeutics, Ind.; Novartis; Novocure; Pfizer; PharmaMar AG; Promontory Therapeutics; Regeneron Pharmaceuticals Inc.; Sanofi; Seattle Genetics; Takeda Pharmaceutical Company Limited; and Vaccibody. All fees to institution.Grant/Research Support from (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen Inc.; AstraZeneca; Biodesix, Inc.; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; F. Hoffmann-La Roche/Genentech; GlaxoSmithKline; Illumina, Inc.; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Mirati Therapeutics, Inc.; Novartis; Pfizer; and Phosplatin Therapeutics.Other Financial or Material Support for talks in a company's organized public event from AstraZeneca; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; ecancer; F. Hoffmann-La Roche/Genentech; Illumina, Inc.; Lilly; Merck Sharp and Dohme Corp.; Novartis; Pfizer; Sanofi; and Takeda Pharmaceutical Company Limited. All fees to institution. On the Board of Directors for Galencia SA.Faculty/PlannerJacob Sands, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Boehringer Ingelheim; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; Lilly; Medtronic; PharmaMar, and Sanofi.Grant/Research Support from Amgen Inc. and Harpoon Therapeutics.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/RGD865. CME/AAPA credit will be available until February 28, 2025.Leveraging TROP2 Expression in NSCLC: Expert Perspectives on the Present Evidence and Future Potential of TROP2-Targeting ADCs in Lung Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerCharu Aggarwal, MD, MPH, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; BeiGene; Blueprint Genetics; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo/AstraZeneca; Eisai; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck and Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./Sanofi; Shionogi Inc.; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; Macrogenics, Inc; and Merck Sharpe and Dohme LLC.Faculty/PlannerProf. Solange Peters, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; Arcus Biosciences; AstraZeneca; Bayer AG; BeiGene; BerGenBio; Biocartis; BioInvent; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; Daiichi Sankyo Co., Ltd.; Debiopharm International SA; ecancer; Elsevier; F. Hoffmann-La Roche/Genentech; F-star Therapeutics Inc.; Fishawack Health Group; Foundation Medicine, Inc.; Genzyme; Gilead Sciences Inc.; GlaxoSmithKline: HUTCHMED; Illumina, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; IQVIA Inc.; iTeos Therapeutics; Janssen Global Services, LLC; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Merrimack; Mirati Therapeutics, Ind.; Novartis; Novocure; Pfizer; PharmaMar AG; Promontory Therapeutics; Regeneron Pharmaceuticals Inc.; Sanofi; Seattle Genetics; Takeda Pharmaceutical Company Limited; and Vaccibody. All fees to institution.Grant/Research Support from (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen Inc.; AstraZeneca; Biodesix, Inc.; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; F. Hoffmann-La Roche/Genentech; GlaxoSmithKline; Illumina, Inc.; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Mirati Therapeutics, Inc.; Novartis; Pfizer; and Phosplatin Therapeutics.Other Financial or Material Support for talks in a company's organized public event from AstraZeneca; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; ecancer; F. Hoffmann-La Roche/Genentech; Illumina, Inc.; Lilly; Merck Sharp and Dohme Corp.; Novartis; Pfizer; Sanofi; and Takeda Pharmaceutical Company Limited. All fees to institution. On the Board of Directors for Galencia SA.Faculty/PlannerJacob Sands, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Boehringer Ingelheim; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; Lilly; Medtronic; PharmaMar, and Sanofi.Grant/Research Support from Amgen Inc. and Harpoon Therapeutics.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

Drs. Shaalan Beg and Rachna Shroff discuss key abstracts on GI cancers that were featured at the 2024 ASCO Gastrointestinal Cancers Symposium, including SKYSCRAPER-08, EMERALD-1, and NEST-1 in esophageal squamous cell carcinoma, hepatocellular carcinoma, and colorectal cancer, respectively. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. Today, we'll be discussing key abstracts and other exciting highlights from the 2024 ASCO Gastrointestinal Cancers Symposium. Joining me to discuss some key takeaways from the meeting is the chair of this year's Symposium, Dr. Rachna Shroff. Dr. Shroff is the division chief of Hematology Oncology and chief of GI Medical Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for clinical and translational research at the University of Arizona College of Medicine – Tucson. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Shroff, welcome back to the ASCO Daily News Podcast, and congratulations on a great Symposium. The scientific advances and innovative, multidisciplinary approaches that were featured throughout the meeting were really inspiring and reflect the incredible strides we're making in GI cancer research. Dr. Rachna Shroff: Thank you so much for having me back. I am delighted to be here.  Dr. Shaalan Beg: Dr. Shroff, the theme of this year's symposium was "Taking Personalized Care to the Next Level." I'd love to hear your reflections on the sessions that you found most exciting and really resonated with the attendees.  Dr. Rachna Shroff: Yes, thank you. We were really excited about this theme because we really felt that “Taking Personalized Care to the Next Level” translated to thinking through personalized approaches to patient care, not just in the traditional ways that we think of with precision oncology and genomics driving our care, but also how we can think through multidisciplinary approaches and an individualized care plan. Thinking through how artificial intelligence and novel clinical trial designs can and should be implemented to meet the needs of our individual patients. And so we really highlighted that in what was a somewhat new reboot of a session called “Intersections,” which were every day and were really more cross-tumor; they were tumor agnostic but were thematic focused. As I mentioned, those themes were really based on feedback that we had from prior attendees, as well as from the program committee's feeling on what are really the questions that we are dealing with and that are burning in the clinic today and that includes the emerging role of artificial intelligence and machine learning and how we integrate that into our clinical care, approaches to oligometastatic disease, and it's not really just something that we think of in colorectal cancer but haven't fully used that paradigm to really apply it to other GI malignancies. And then the art and science of clinical trial design where, again, traditional randomized phase 3 trials might not be the best and most innovative and most expedient way of bringing novel therapeutics to our patients. And so, I thought that all of those sessions were really highlighting different important topics that we deal with day to day. Additionally, we had a really fantastic keynote lecture from Dr. Kimmie Ng of the Dana-Farber Cancer Institute. She is a world-renowned expert in the early-onset colorectal cancer space, and the timing of her keynote was perfect with the new cancer statistics that came out literally days before GI ASCO that demonstrated this just dramatic rise in early onset GI malignancies as a whole, not just colorectal. And she spoke really in a comprehensive manner not just on clinical approaches, screening approaches, and how to find these patients at an earlier stage, but also kind of gave us a call to action, if you will, in terms of public health initiatives, as well as like I said, clinical care and really thinking outside of the box for how to reach these patients.  And then, of course, we always have what I think is one of my favorite aspects of the meeting, which are the networking opportunities that include the Trainee and Early Career Networking Luncheon, the Women's Networking Reception, and the Meet the Experts Luncheon where, especially as junior career investigators, you have an opportunity to meet what we think of as the “big names” in GI cancer. Dr. Shaalan Beg: Absolutely, I remember my first couple of GI ASCO meetings and those were probably the most memorable sessions that I attended as junior faculty as well.   So let's take a deeper dive into some key abstracts from the meeting. I'd like to begin with Abstract 245. This is the SKYSCRAPER-08 study. It's first-line tiragolumab and atezolizumab with chemotherapy in an Asian patient population with esophageal squamous cell carcinoma. What are your key takeaways from this study?  Dr. Rachna Shroff: Yeah. This was an exciting study in my opinion in the sense that thinking through how we can build on immunotherapy backbones is obviously a pressing question across the GI cancer space. So this was a phase 3 randomized, double-blinded, placebo-controlled trial that looked specifically at patients with esophageal squamous cell carcinomas. And the study was enrolled fully with an Asian population. It looked at taking the traditional chemotherapy backbone and adding to it an anti-PD-L1 with atezolizumab and an anti-TIGIT with tiragolumab. Again, that proof of principle of using anti-TIGIT and PD-L1 has been looked at across a lot of different GI cancer spaces and we know that the esophageal squamous cell cancers tend to be very immunotherapy responsive. So this was a really important question.  This involved a number of patients, a little over 460 patients, who were randomized one-to-one to receive the tiragolumab with atezolizumab with the standard paclitaxel and cisplatin, that's used for esophageal squamous versus chemotherapy alone with placebo. And the primary endpoint was independent review of progression-free survival, and overall survival. And so, out of the 461 patients randomized, there was at the primary analysis, a median improvement in progression free survival, from 5.4 months in the control arm to 6.2 months with a tira-paclitaxel plus chemo arm with a hazard ratio of 0.56, highly statistically significant. Similarly the median overall survival was also improved from 11.1 months to 15.7 months again with a hazard ratio of 0.7 and some of the other key efficacy endpoints were also improved with the addition of the anti-TIGIT PD-L1 approach. And importantly, there was not really safety signals that jumped out at us.  And so, to me, what this means is that, in our patients with esophageal squamous cell carcinoma, we really should be thinking about chemotherapy with immunotherapy as a backbone and how we can build on it. And, you know, I would imagine that it's hard to argue with both the PFS and OS endpoint that adding anti-TIGIT won't necessarily be kind of the new approach to these patients. And importantly, I'll point out that it seems to be a benefit across the subgroups, including PD-1 status, which is always our big question here. I think the only thing to keep in mind is this was an all-Asian population and whether or not that kind of immune profile of the immune responsiveness is different in those patients, but regardless, a positive phase 3 trial. Dr. Shaalan Beg: It's really exciting to see immune checkpoint inhibitors or immunotherapy beyond PD-1 targeted, CTLA-4 targeted treatments making their way into GI Cancers.  Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: Sticking with the immunotherapy theme, let's focus on hepatocellular carcinoma. So LBA432, the EMERALD-1 study of transarterial chemoembolization combined with durva with or without bevacizumab looked at people with unresectable hepatocellular carcinoma eligible for embolization. So really a highly anticipated study, I'm wondering what your thoughts are and whether it'll be practice-changing for this field.  Dr. Rachna Shroff: I was excited to see the press release when it showed that the study was positive, and I think it's because now that we're using immunotherapy in the advanced HCC space, our obvious question is, can we integrate it into multimodality approaches? There are a lot of smaller studies looking at neoadjuvant IO approaches, and in this intermediate stage, unresectable hepatocellular carcinoma patients. We wanted to know if there was a utility to liver directed therapy with immunotherapy.  So, this was a large study. It was a global study looking at unresectable HCC with preserved Child-Pugh function. But it was Child-Pugh A and up to B7, importantly. And there were 616 patients randomized in a 1:1:1 fashion, with the control arm being just TACE alone. But then, there was also an opportunity for durvalumab with TACE, as well as durvalumab plus bevacizumab with TACE. The patients would receive durvalumab during their TACE treatments and could receive up to four TACE treatments and then subsequently were either continued on durvalumab alone, durvalumab plus bevacizumab, or the placebo. The primary endpoint was progression-free survival, powered specifically to look at TACE versus durvalumab plus TACE. In this study, the primary endpoint was met with a significant improvement in PFS. Median PFS was 15 months versus 8.2 months, with a hazard ratio of 0.77. Most prespecified subgroups demonstrated this benefit.  Importantly, there was a secondary endpoint looking at durvalumab plus TACE versus TACE alone, and that actually did not show a statistically significant improvement in median PFS from 8.2 months in the control arm to 10.0 months. The overall response rates were slightly higher with the durvalumab plus bevacizumab approach at 43.6%. And importantly in these patients, who oftentimes have a higher burden of disease in the liver, median time to progression is a really important and clinically meaningful endpoint. That was 22 months with the durvalumab plus bevacizumab and TACE versus 10 months for TACE alone. I would just point out that the overall concern we always have with bevacizumab is the increased risk of bleeding and the treatment-related adverse event profile. Overall, there were no safety signals that emerged from this, with nothing that really, especially in that bleeding risk category, jumped out at us. Of course, we haven't seen the overall survival data yet because we have not seen enough follow-up to really see that number.  I do think that this is potentially practice-changing, and I think it just demonstrates that there's probably some synergy between anti-VEGF with anti-PD-1, and then the liver-directed treatments. The obvious question for us in the United States is that the vast majority of people are moving away from TACE and towards more radioembolization and what can we extrapolate from this? Does this really tell us much if people are using more of a Y90-based approach? I think those are a lot of the burning questions that most of us have.  Dr. Shaalan Beg: Yeah, and it's a very interesting direction that the HCC space is taking because we heard in previous meetings, the role of PD-1 inhibition as adjuvant therapy after resection. Now, we have data for local-regionally advanced disease over local-regional treatments. And of course, you already mentioned the data for more advanced disease. So it sounds like immunotherapy may be impacting the management of anyone diagnosed with hepatocellular carcinoma.  Let's talk about the MONET trial, Abstract 249, which compared thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer. Do you think this is a study which may influence the treatment of patients with thoracic esophageal cancer? Dr. Rachna Shroff: So, this was, again, I think, a really important question. It was a randomized, controlled phase 3 trial comparing a more minimally invasive approach with TE — thoracoscopic esophagectomy — versus an open approach. This had patients with clinical stage 1-3, excluding T4 thoracic esophageal squamous cell carcinomas. They were randomized 1:1 to the open versus the TE approach, with a primary endpoint of overall survival and an important secondary endpoint of relapse-free survival. 300 patients were randomized, and at the second planned interim analysis, the median follow-up was a little over two and a half years. The 3-year overall survival was 82% in the TE group versus 70.9% in the open group. The DSMC of this trial actually recommended early termination based on the non-inferiority, which is what they were specifically looking at. There was a very statistically significant one-sided p-value for non-inferiority.  Importantly, the 3-year recurrence-free survival was also markedly better in the TE group versus the open group, with no real notable differences in R0 resection, or a large percentage of patients who needed to be converted from a TE to an open approach, and really not any significant difference in overall postoperative morbidity. I think this just supports the concept that minimally invasive approaches for our patients with GI malignancies can and should be considered. Again, esophageal squamous because they tend to be seen a lot more in Asia, this study was conducted in Japan, but I think that being said, a lot of our surgeons in Europe and in the U.S. are also very amenable to minimally invasive approaches. And I think this just supports the fact that an open approach is not necessary. So, I would think again, that this is something that is implementable and I think will affect the field.  Dr. Shaalan Beg: Moving on to metastatic cholangiocarcinoma, there have been many FGFR inhibitors that have shown activity and promise and are approved for the management of cholangiocarcinoma with FGFR alteration. But at this ASCO GI, we heard the results of the safety and efficacy of an FGFR1, 2, and 3 inhibitor, tinengotinib, as monotherapy for advanced metastatic cholangiocarcinoma (Abstract 434). How do you see this fitting into the broad picture? Dr. Rachna Shroff: Yeah, so this was highly anticipated data, primarily because at this point, the FGFR space in cholangiocarcinoma is quite crowded. And so a lot of us were getting sick of the "me-too" drugs. What is really unique about tinengotinib is that, not only is it a selective multikinase inhibitor, but it also, in preclinical models as well as in early phase one trials, demonstrated potent inhibition of patients with FGFR2 fusions and rearrangements who had acquired resistance mutations. So, as we better understand the first generation of FGFR inhibitors and note the resistance mechanisms, these drugs are now being developed to try to circumvent or overcome those.  This study looked at 4 different cohorts: 1 cohort with FGFR2 fusion patients who had primary progression who never responded to FGFR inhibitors, a second cohort with FGFR2 fusion patients who had progression after primary response, so those with acquired resistance, and then there was non-fusion FGFR alterations because we do know that a number of cholangiocarcinoma patients have other FGFR alterations that are not fusions, and then those with FGFR wild-type. The primary endpoint was objective response rate, with a total of 48 patients enrolled across the four cohorts. And so the 40 patients who were evaluable in the group that had primary resistance, which was the first cohort, there was a response rate was 9.1% and that was partial response, and 31% had tumor reduction with tinengotinib. And similarly in those with acquired resistance, 37.5%, 3 out of 8 patients had a partial response and tumor reductions were noted with an overall disease control rate between those patients with FGFR2 fusions of 94.7%, between those with primary and secondary resistance.  In the patients who had FGFR alterations, there was 3 out of 9 patients with a partial response and again, tumor reductions were notable across the board and the disease control rate was 88.9%. The FGFR wild-type group, not surprisingly, did not see any partial responses, but interestingly, 75% of these patients had at least disease control, and the median progression-free survival was 5.26 months, again, kind of most notably impressive in the 2 cohorts that included FGFR2 fusions. The toxicity profiles are what we come to expect for FGFR inhibitors and we've gotten better at managing those and mitigating some of those so there was really nothing to jump out there. So there is now an ongoing randomized phase III trial specifically looking at tinengotinib versus physician's choice in patients with FGFR2-altered cholangiocarcinoma after having received prior FGFR inhibitors. So that's where I think it's in is for those of us who know that there are multiple drugs in the space, our big question is can we sequence through that? Can we offer multiple FGFR inhibitors in these patients? And I think we are all eagerly anticipating this data as well as the subsequent data to really justify the use of these novel second generation FGFR inhibitors.  Dr. Shaalan Beg: It's been fantastic to see the evolution of these compounds in precision medicine, or precision oncology at its finest, in terms of understanding mechanisms of resistance and treating refractory disease.   Let's focus on colorectal cancer. I'll tell you, there has been a lot of discussion, Dr. Shroff, on social media, on insurance companies sometimes rejecting one biologic or the other based on tumor sidedness. We have talked about tumor sidedness predicting response on this podcast based on data from previous studies. But this year in GI ASCO, Abstract 207 explored the role of tumor genomics and tumor sidedness and they said that it's tumor genomics, that tumor genomics better explains the differences on outcomes, and it explains it better than sidedness. What does this mean to the field? Because a lot of professional organizations have guidelines that are asking people to now incorporate sidedness. So how does that change based on these results? Dr. Rachna Shroff: I really commend these authors on leveraging real-world data, and I think we're getting better and better at recognizing that real world data actually informs our clinical decision making, possibly better than sometimes some of these studies that lead to the guidelines and algorithms that we develop. So this is a perfect example of a little bit cart before horse in trying to understand the way that sidedness and genomics may interplay.   So this was a study that basically leveraged both the Foundation Medicine and Flatiron Health clinical genomic database and looked at patients with microsatellite stable metastatic colorectal cancer. There were a total of 3,845 patients included in a kind of two-thirds one-third split between left sided and right-sided colorectal cancer. And they found the typical genomic alterations that historically have been thought of more with left-sided colorectal cancer like APC and then more of the RAS BRAF alterations in the right-sided patients. But I think what they really thought and what I think was remarkable is they really looked at the patients and how they received chemotherapy with anti-EGFR or bevacizumab therapies, and they did a multivariate analysis to really see what is driving outcomes. And like you mentioned, what they found was patients in the RAS pathway, those classified as having alterations in the RAS pathway, had less favorable outcomes, while those with APC altered group had more favorable outcomes. And that was regardless of treatment received and sidedness.  And so when they did an analysis of what was called a “likelihood ratio test,” they found that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction, but not when sidedness was added to genomics. Like you said, it kind of demonstrates, at least in this mining of real-world data from Flatiron that tumor genomics is probably a better driver and a more important driver in determining outcomes than sidedness.  I totally agree with you. I would push for us to really kind of bring a little bit of noise to this and to make insurance companies and other companies that are looking at this to think through this a little bit more and make sure that we're putting all of the data together in a comprehensive passion before making the treatment plans and determinations. Dr. Shaalan Beg: The last abstract I'd like to ask you about is Abstract 117, the NEST-1 trial. This study looked at neoadjuvant botensilimab and balstilimab for resectable mismatch repair proficient and deficient colorectal cancer, both MSS and MSI. What are your key takeaways from this study?  Dr. Rachna Shroff: This is another study that is demonstrating that there may potentially be a role for immunotherapy in microsatellite stable patients. I will make the caveat that this was a single-arm study that really was looking at feasibility safety, with efficacy as a secondary endpoint. The combination of bot-bal in the neoadjuvant space for colorectal cancer patients, they received one dose of boten and two fixed doses of bal two weeks apart and then were taken to surgery. They limited the number of patients and out of the 12 patients that were enrolled, they limited the number of mismatch repair deficient patients. So to your point, they allowed both, but they wanted to make sure it was not just MSI-high patients. What they basically found is that it was safe and did not delay surgery or increase risks of adverse events. But importantly, there was significant regression of tumor noted. And some interesting spatial biology analyses demonstrated potentially novel mechanisms of action, especially in the MSS population, and that ctDNA reductions correlated with pathologic response. There were a lot of different things that they were looking at, basically suggesting that bot-bal is safe and can be used in both mismatch repair–deficient and proficient patients with colorectal cancer. And now importantly, they've added some additional cohorts and expanding the study. As I mentioned, this is right now just 12 patients, but does definitely have a provocative result.  Dr. Shaalan Beg: Thanks so much, Dr. Shroff.  Finally, the role of cell-free DNA (cfDNA) in GI cancers has been an exciting and important development in our field. There's tremendous data that emerged at the GI meeting, and we have decided to do a separate ASCO Daily News Podcast dedicated to ctDNA. So listeners, please look out for our coverage of key studies on ctDNA in GI cancers very soon here on the ASCO Daily News Podcast.  Many thanks, Dr. Shroff, for sharing your insights with us today and for your great work in building a robust GI meeting this year. Thank you very much. Dr. Rachna Shroff: Thank you so much. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: 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. Our guests on this podcast express their own opinions, experiences, and conclusions. These statements do not necessarily reflect the views of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an endorsement by ASCO.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EGP865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until December 12, 2024.Equitably Empowering Our Upper GI Cancer Patients Using Plain Language Tools to Improve Outcomes With Immunotherapeutic Regimens Through Informed Shared Decision-Making In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an educational grant from Bristol Myers Squibb.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck & Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck & Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PZU865. CME/NCPD/CPE/AAPA/IPCE credit will be available until November 27, 2024.Elevating Outcomes for HER2-Expressing GI Cancers: The Evolving Role of Molecularly Targeted Agents in BTC and GEA Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program is supported by an independent medical education grant from Jazz Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosep Tabernero, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Cardiff Oncology, Inc.; CARsgen Therapeutics; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Genentech Inc; hC Bioscience, Inc.; Ikena Oncology; Inspirna, Inc.; Lilly; Menarini; Merck Serono; Merck Sharp & Dohme; Merus; Mirati Therapeutics Inc.; NeoPhore; Novartis AG; Ona Therapeutics; Orion Biotechnology; Peptomyc; Pfizer; Pierre Fabre; Samsung Bioepis; Sanofi; Scandion Oncology A/S; Scorpion Therapeutics; Seagen; Servier; SOTIO Biotech AG; Taiho; Takeda Oncology, ; and TOLREMO Therapeutics AG.Stock Shareholder in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP.Co-Chair/PlannerShubham Pant, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AskGene Pharma Inc.; Boehringer Ingelheim International GmbH; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; and Zymeworks Inc.Grant/Research Support from 4D Pharma; Amal Therapeutics; Arcus Biosciences; Astellas Pharma Inc.; BioNTech; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Elicio Therapeutics; Immuneering Corporation; ImmunoMET; Ipsen Pharma; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; NGM Biopharmaceuticals; Novartis Pharmaceuticals Corporation; Pfizer; Purple Biotech; Rgenix; Xencor; and Zymeworks Inc. All goes to Institution.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. CME/MOC/AAPA credit will be available until November 13, 2024.Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Speaker for AstraZeneca; Daiichi Sankyo, Inc.; and F. Hoffmann-La Roche Ltd/Genentech, Inc.Faculty/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, lnc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biophanna Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, lnc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer lngelheim Pharmaceuticals, lnc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serano, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; lmmunoGen, Inc.; lmmunomedics, Inc.; lncyte; Infinity Pharmaceuticals, Inc.; lnvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, lnc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; Medlmmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove lnc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr lmmunotherapeutics; Plexxikon; Radius Health, lnc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen lnc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, lnc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; Taplmmune lnc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks (all paid to institution).Faculty/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck and Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck and Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Faculty/PlannerAntonio Passaro, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; GSK; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Sharp and Dohme; Mundipharma International; Novartis AG; Pfizer; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ArriVent Biopharma; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Serono; Merck Sharp and Dohme; Mirati Therapeutics, Inc.; Pfizer; and RMC Pharmaceutical Solutions Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. CME/MOC/AAPA credit will be available until November 13, 2024.Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Speaker for AstraZeneca; Daiichi Sankyo, Inc.; and F. Hoffmann-La Roche Ltd/Genentech, Inc.Faculty/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, lnc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biophanna Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, lnc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer lngelheim Pharmaceuticals, lnc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serano, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; lmmunoGen, Inc.; lmmunomedics, Inc.; lncyte; Infinity Pharmaceuticals, Inc.; lnvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, lnc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; Medlmmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove lnc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr lmmunotherapeutics; Plexxikon; Radius Health, lnc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen lnc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, lnc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; Taplmmune lnc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks (all paid to institution).Faculty/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck and Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck and Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Faculty/PlannerAntonio Passaro, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; GSK; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Sharp and Dohme; Mundipharma International; Novartis AG; Pfizer; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ArriVent Biopharma; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Serono; Merck Sharp and Dohme; Mirati Therapeutics, Inc.; Pfizer; and RMC Pharmaceutical Solutions Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. CME/MOC/AAPA credit will be available until November 13, 2024.Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Speaker for AstraZeneca; Daiichi Sankyo, Inc.; and F. Hoffmann-La Roche Ltd/Genentech, Inc.Faculty/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, lnc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biophanna Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, lnc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer lngelheim Pharmaceuticals, lnc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serano, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; lmmunoGen, Inc.; lmmunomedics, Inc.; lncyte; Infinity Pharmaceuticals, Inc.; lnvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, lnc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; Medlmmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove lnc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr lmmunotherapeutics; Plexxikon; Radius Health, lnc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen lnc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, lnc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; Taplmmune lnc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks (all paid to institution).Faculty/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck and Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck and Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Faculty/PlannerAntonio Passaro, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; GSK; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Sharp and Dohme; Mundipharma International; Novartis AG; Pfizer; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ArriVent Biopharma; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Serono; Merck Sharp and Dohme; Mirati Therapeutics, Inc.; Pfizer; and RMC Pharmaceutical Solutions Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. 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Drs. Shaalan Beg and Priyanka Kanth discuss the readiness, logistics, and barriers to implementing universal germline multigene panel testing for colorectal cancer (CRC) following new guidelines from the National Comprehensive Cancer Network that recommend genomic testing for all individuals with CRC younger than age 50. The experts also address other areas of unmet needs as new data emerge on moderate-risk genes and their association with CRC. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm the vice president of oncology at Science 37 and an adjunct associate professor at UT Southwestern Medical Center in Dallas. Last year, the National Comprehensive Cancer Network, or NCCN, updated its guidelines on colorectal cancer (CRC), recommending that all patients with colorectal cancer who receive a diagnosis before the age of 50 have multigene panel testing and that multigene testing should also be considered for patients 50 years of age and older with colorectal cancer, regardless of a personal or family history or other criteria. This represents a huge paradigm shift in the screening and care of patients with inherited cancers. And today, I'm joined by Dr. Priyanka Kanth, an associate professor of medicine and the director of the GI Cancer Prevention Program at MedStar Georgetown University Hospital in Washington, DC, to discuss new research that explores the readiness, logistics, and barriers associated with the implementation of universal germline testing in clinical practice.  You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod. Dr. Kanth, it's great to have you on the podcast today. Dr. Priyanka Kanth: Thank you, Dr. Beg. It's wonderful to be here today and discuss this very exciting topic. Dr. Shaalan Beg: As a gastroenterologist who sees patients and families with a high risk for GI cancer, including medically underserved populations, can you comment on the significance of the expanded NCCN guidelines for colorectal cancer? Dr. Priyanka Kanth: Yes, absolutely. So this is, I would say, a big change from NCCN recommending pretty much every colorectal cancer patient can undergo multigene panel testing or universal. So everyone who's younger than age 50 and has colon cancer should get multigene panel testing. But we are also expanding it to pretty much anyone who may have colorectal cancer, and we can offer multigene panel testing. So, we are broadening the pool of patients who can get tested, and this will bring in more patients from very different demographics. So I think it will expand to every arena of patients with different insurance profiles, underserved, and, as more insurance companies and Medicare/Medicaid picks up, I think this will help a lot more patients in not only following on their genetic testing, but also their family members.  Dr. Shaalan Beg: Medical oncologists are very familiar with the challenges of implementing somatic molecular testing for people who have cancer. I can only imagine that implementing universal germline testing also has significant logistical challenges and barriers. You recently published a study in JCO Precision Oncology along with your colleagues and captured some interesting perspectives from clinicians on their practice of implementing universal genomic testing for colorectal cancer. Can you tell us more about this? Dr. Priyanka Kanth: Absolutely. So I would first like to thank the lead authors and senior authors of this study. They are Linda Rodgers-Fouche and Sanjeevani Arora and Rachel Hodan, who literally wrote the study and created and did all the legwork. And as you know how hard it is to do these big survey studies, so really thank them.  The study is a cross-sectional survey of the members of this Community Collaborative Group of America, IGC, which I would say comprises a lot of genetic counselors, gastroenterologists, oncologists, and colorectal surgeons who take care of these patients. So these are highly specialized groups that work in the field of GI genetics. Roughly 300 plus members were sent the survey to get their take on how they think [multigene panel testing] can be implemented for all colorectal cancer patients.   So to give you a synopsis of the study, the majority of members who participated, 70% or more, they supported this universal germline testing for colorectal cancer patients. But interestingly, more than 50% also thought that it will require a change in their practice or how this will be delivered. So that's the major takeaway, I would say. We are all supportive but how to really deliver to the patient would be the biggest challenge or barrier for us in the future.  Dr. Shaalan Beg: So, your study reported concerns on knowledge among non-genetics providers. I would assume that includes a lot of clinicians who are the first people to be in contact with potential patients who would require testing. How can the field mitigate this problem? And what are some alternate delivery service models for increasing awareness and making the process of ordering and following up on the results more efficient for practices? Dr. Priyanka Kanth: We all know the biggest barrier I would say is resources like who's going to deliver the added pool of patients that get genetic testing. So most of the current scenario, they're all seen by genetic counselors, but we have a limited number of genetic counselors and they cannot truly deal with this big influx. So how to educate non-genetic providers would be the biggest barrier. But also implementing in the system itself, like can we do pretest counseling as the first contact with the patient to deliver to discuss like you should undergo genetic testing. So that contact, can that be done with a non-genetic provider or even by other modes like telemedicine? Or can we do something like an online chat box or something which could just not only go over all the types of testing but opens the door for the patient to ask questions. So if there are alternate modes of delivery where the pretest is taken care of, that would be one big change required.   The other part is like when the test is done, who returns the results? So where does it go and who explains the results? So at that point, we surely need more genetic and even non-genetic providers if they are comfortable. So how to educate them would be the biggest barrier. At that point, I think, we are still figuring out the biggest change is in the system and requiring a take from all the stakeholders who are part of taking care of these patients. So not only genetic counselors, but oncologists, gastroenterologists, pathologists who are taking care of this patient to be on board and have a really clear-cut flow of how these are delivered, how these results are returned, and how they are explained to family members. Dr. Shaalan Beg: The workflows and the resources that you have in a high-risk GI clinic at a center like Georgetown's, I think it's safe to say, are much more than what typical resources a practicing provider will have in the clinic. How do you envision clinics resourcing for this type of test either through training or retraining their existing staff or by adding additional resources?  Dr. Shaalan Beg: At the community setting, it is really hard to educate essentially everyone as well. So, I feel like taking the load off the genetic counselor at the pretest level is the biggest implementation or change that can be done. And if we can remove that because not every patient is going to be positive for the gene mutation either; it does filter many patients who eventually will need returns. So at that place, how do you implement and where do you implement is the key and it is so system-based that I cannot even pinpoint. But I agree, bigger academic centers have better advantages and a knowledge base as compared to smaller community cancer centers or practices. Dr. Priyanka Kanth: Yeah, and I noticed that many of the respondents in your survey agreed with offering multigene panels, but there was variability by profession, and I was wondering if that resonated with you and that was an expected finding or not. Dr. Priyanka Kanth: Yes, and it was more so in terms of standardized multigene panel versus customized panel. So, this is fairly understandable because the genetic counselor is so well versed in offering which genes should be tested based on family history, but a non-genetic provider may not be fully equipped with the knowledge. So for example, myself, I do GI genetics, but if I have a patient with a lot of breast cancer in the family, I do defer them to a high-risk breast team. So there are nuances, too. The major difference here was also in standardized multigene panel, most of the gastroenterologists, oncologists were all for it compared to customized, which were more heavily leaned by the genetic counselor based on family history. And I can see why it's different because standardized, I would say, is much easier to implement and compared to customizing, which is based on family history or other cancer history and family. That's the major difference in the study. It comes down to education and experience and the follow-up based on what comes back from it.   Dr. Shaalan Beg: You've highlighted many factors, both from the pre-test, sort of preparing and selecting the right individuals, to ordering the right test based on the participant's risk factor profile and then optimal ways of following up on the results of these genomic tests. What are other areas of unmet needs when it comes to genomic testing for colorectal cancer? Dr. Priyanka Kanth: We know a lot about high-risk genes that are associated with colorectal cancer. We still are finding and learning about many genes, many moderate-risk genes, and their association with colorectal cancer. We don't have enough data or long-term cohort data to understand how they truly affect their lifetime risk for colorectal cancer and how do we truly surveil these patients. So that's one of the big barriers. Genetics still cannot explain all colorectal cancers. So as we get more data, we may discover more things and more genes that may be associated. But understanding these moderate-risk genes and their association with colorectal cancer would be, I think, one of the key areas to be looked into in the future. Dr. Shaalan Beg: And I would imagine as new biomarkers are identified, there will need to be a strategy to retest people who may have had genomic testing in the past. Dr. Priyanka Kanth: Absolutely. We are already encountering that in a practice. I have patients who have been tested maybe 10 years ago and just had Lynch mutation tested and were negative for that or so, and now we have so many other genes which are associated and also to understand family history changes. So, as family history changes, there might be clues to say that, “Okay, we should expand the panel or we should add these patients.” So it is a very dynamic situation. There could be a scenario in which we have a lot of patients who may need to be retested based on their current situation or even based on changing family history and the availability of genetic information. So, when I see a patient, I also tell them if we don't find anything or we are not doing anything major, we say, “Let's regroup in 3 to 5 years, let's see where we are,” or even with the risk mutation for some of the moderate-risk genes, we may change in a few years. So, revisiting that with these patients is highly useful. Dr. Shaalan Beg: So, is it safe to say that as of 2023, if we're seeing people in our clinic who have not had testing in the last 3 to 5 years, that they should have a discussion for repeat testing today? Dr. Priyanka Kanth: Yes, in terms of certain, I would say, newer polyposis genes in the GI world that have been included, some other moderate gene mutation which we have a little bit more sense of now and it has not been tested, I think that can be expanded. Five years is a safe bet. Last 2 to 3 years, maybe not so much, but you can revisit this. Also, some patients were tested for a smaller gene panel. So not 2 genes, but maybe 10 genes were included. That would probably still stand true. They may not need 70 gene panels, so it's still good to review that in the current scenario, and every few years, every 5 years, I would say.   Dr. Shaalan Beg: Whenever I think about any type of new test that has logistical challenges, has costs associated with it, and has operational demands of the clinic, I think about its disparate effect across different populations based on race, ethnicity, geography, demographics. Can you talk a little bit about how these guideline changes, what type of impact they may have, positive or not, for comprehensive genomic testing for colorectal cancer across different populations?  Dr. Priyanka Kanth: Yes, I think this is more positive than negative. This will include more patients and include more family members who were not being included, who were being missed. As we know that one of the reasons to do this multigene panel testing was the criteria, the family history criteria or the risk prediction models are not perfect. And the recent studies have shown that not every family member, every patient, is going to fit in these criteria. So we are getting more and more data in recent years that I think the much better, long-term option is to do a multi-chain panel and find it because we are missing patients. So it will increase the pool [of patients to be tested], and that will surely increase patients from all demographics. And as we do it more, there will be more buy-in from the payers and hopefully, this will decrease disparity. The problem, I think the negative part is how do we deliver it to everyone? If it is there but we are not able to deliver and that there is disparity on who gets the test and who does not, then that will create another disparity in a sense that it's there and we could have used it, but it's not being delivered. So the pros are we can include everyone, but how to include everyone is the big question. Dr. Shaalan Beg: So, Dr. Kanth, there are indeed challenges ahead in our pursuit for universal germline testing for colorectal cancer. I'd like to thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast.   Dr. Priyanka Kanth: Thank you very much for having me here. It was great to talk to you, Dr. Beg. Dr. Shaalan Beg: And thank you to our listeners for your time today. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer:  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. Find out more about today's speakers:   Dr. Shaalan Beg @ShaalanBeg   Dr. Priyanka Kanth @priyanka_kanth   Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook  ASCO on LinkedIn    Disclosures:   Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Priyanka Kanth:  Patents, Royalties, Other Intellectual Property: Methods and Compositions for Predicting a Colon Cancer Subtype