Podcasts about folfiri

In a conversation with CancerNetwork®, Marwan G. Fakih, MD, spoke about the FDA approval of sotorasib (Lumakras) plus panitumumab (Vectibix), and how it may affect the treatment paradigm for patients with KRAS G12C-mutant metastatic colorectal cancer (CRC). Fakih is a professor in the Department of Medical Oncology & Therapeutics Research, associate director for Clinical Sciences, medical director of the Briskin Center for Clinical Research, division chief of GI Medical Oncology, and co-director of the Gastrointestinal Cancer Program at City of Hope Comprehensive Cancer Center in Duarte, California. According to Fakih, the approval of this combination regimen is a “welcome step” for those with metastatic CRC harboring KRAS G12C mutations. Based on supporting data from the phase 3 CodeBreaK 300 trial (NCT05198934), sotorasib/panitumumab may prolong progression-free survival (PFS) and reduce disease burden in patients while offering improvements in other outcomes vs prior standards of care (SOC) like trifluridine/tipiracil (Lonsurf) and regorafenib (Stivarga). Topline data at the time of the approval showed a median PFS of 5.6 months (95% CI, 4.2-6.3) with sotorasib at 960 mg plus panitumumab vs 2.0 months (95% CI, 1.9-3.9) in the SOC arm, in which patients were assigned to receive trifluridine/tipiracil or regorafenib (HR, 0.48; 95% CI, 0.30-0.78; P = .005). Additionally, the overall response rate was 26% (95% CI, 15%-40%) vs 0% (95% CI, 0%-7%) in each respective arm. Looking ahead, Fakih highlighted the potential next steps for research associated with the sotorasib combination as well as other novel therapeutic strategies in the gastrointestinal cancer space. For example, he described the phase 3 CodeBreaK 301 study (NCT06252649), which will evaluate sotorasib/panitumumab as frontline therapy when administered in combination with folinic acid, fluorouracil, and irinotecan (FOLFIRI) vs FOLFIRI plus bevacizumab (Avastin) in metastatic KRAS G12C-mutant CRC. Other novel agents under development in the space include RAS inhibitors and immunotherapy regimens combining CTLA-4 inhibitors with anti–PD-L1 agents. References 1. FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. News release. FDA. January 16, 2025. Accessed February 12, 2025. https://shorturl.at/1WviB 2. Kim TW, Price T, Grasselli J, et al. A phase 3 study of first-line sotorasib, panitumumab, and FOLFIRI versus FOLFIRI with or without bevacizumab-awwb for patients with KRAS G12C–mutated metastatic colorectal cancer (CodeBreaK 301). J Clin Oncol. 2025;43(suppl 4):TPS326. doi:10.1200/JCO.2025.43.4_suppl.TPS326

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. 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

El Dr. Jorge Gallardo, oncólogo médico, Coordinador de Oncología Médica en la Clínica INDISA en Providencia, Santiago de Chile junto con la Dra. Marytere Herrera Martínez, oncóloga médica adscrita a la Unidad de Tumores Gastrointestinales del Instituto Nacional de Cancerología, en la Ciudad de México, México nos hablan sobre los estudios más relevantes presentados durante el Simposio de Cánceres Gastrointestinales 2024 :   Tubo digestivo KEYNOTE 590: resultado a 5 años del estudio fase III, aleatorizado, doble ciego, que evaluó el uso de pembrolizumab en combinación con quimioterapia (QT) con cisplatino y 5-fluorouracilo vs. placebo + QT como tratamiento de primera línea en pacientes con cáncer esofágico avanzado metastásico. MATTERHORN: estudio fase III, aleatorizado, doble ciego que evaluó el tratamiento de durvalumab o placebo neoadyuvante-adyuvante y QT FLOT (fluorouracilo + leucovorina + oxaliplatino + docetaxel) seguido de durvalumab o placebo adyuvante en pacientes con cáncer resecable de la unión gástrica y gastroesofágica. KEYNOTE 585: estudio fase III, aleatorizado, doble ciego, el cual comparó pembrolizumab perioperatorio más QT vs. placebo perioperatorio más QT en pacientes con cáncer en la unión gástrica o gastroesofágica localmente avanzada. Cabe destacar que se realizó una cohorte en donde se evaluó pembrolizumab + FLOT y los resultados mostraron un aumento en las respuestas patológicas completas con pembrolizumab perioperatorio más FLOT vs. FLOT solo. Tumores neuroendocrinos NETTER-2: estudio fase III, multicéntrico, aleatorizado y abierto que evaluó la eficacia y seguridad de Lu-177 dotatate en combinación con octreótido en pacientes con tumores neuroendocrinos gastroenteropancreáticos (TNE-GEP) con altas tasas de proliferación (G2 y G3). Se observaron mejoras significativas en la supervivencia libre de progresión con la combinación vs. octreótido en dosis elevadas. Carcinoma hepatocelular EMERALD-1: estudio fase III, global, aleatorizado, doble ciego, controlado con placebo que evaluó el uso de durvalumab + quimioembolización transarterial (TACE, por sus siglas en inglés) concurrente, seguido de durvalumab con o sin bevacizumab hasta la progresión, en comparación con TACE solo en pacientes con carcinoma hepatocelular (CHC) irresecable elegibles para embolización. Cáncer colorrectal CheckMate-8HW: estudio fase III, abierto, en el cual se observó una mejora en el objetivo primario de supervivencia libre de progresión (SLP) con la combinación de nivolumab + ipilimumab vs. la QT elegida por el investigador (mFOLFOX-6 o FOLFIRI con o sin bevacizumab/cetuximab) en el tratamiento de 1L para los pacientes con cáncer colorrectal metastásico (CCRm) con inestabilidad de microsatélites alta (MSI-H, por sus siglas en inglés) o deficiencia en la reparación de emparejamiento (dMMR, por sus siglas en inglés). BESPOKE: estudio de cohorte observacional, prospectivo y multicéntrico en el cual se inscribió un total de 2000 pacientes en etapa I-IV y se realizó un seguimiento de los mismos durante un máximo de 2 años con análisis seriados de ctDNA programados con las visitas de atención estándar. Fecha de grabación: 24 de enero de 2024.               Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

Featuring perspectives from Dr Kristen K Ciombor and Dr J Randolph Hecht, including the following topics: Introduction (0:00) Case: A woman in her early 80s with KRAS-mutated, HER2-positive metastatic colorectal adenocarcinoma — Zanetta S Lamar, MD (14:29) Case: A man in his late 70s with metastatic KRAS G12C-mutated rectal adenocarcinoma treated with third-line sotorasib/panitumumab — Georges Azzi, MD (26:03) Cases: A man in his late 50s with KRAS-mutated metastatic colon cancer and very slow disease progression on second-line FOLFIRI/bevacizumab, and a man in his mid 40s with KRAS wild-type metastatic colon cancer and disease progression on third-line treatment — Priya Rudolph, MD, PhD, and Ina J Patel, DO (30:41) Case: A man in his early 80s with right-sided microsatellite-stable (MSS), KRAS G12D-mutated metastatic colorectal cancer (mCRC), tumor mutational burden 10 mut/Mb, currently receiving third-line TAS-102 — Warren S Brenner, MD (37:11) Case: A man in his late 70s with microsatellite instability-high, BRAF V600E-mutated recurrent cecal adenocarcinoma — Nikesh Jasani, MD (50:09) Cases: A woman in her late 50s with MSS BRAF V600E-mutated mCRC with brain and bone metastases who experiences a good response to dose-reduced FOLFOX after disease progression on first-line encorafenib/cetuximab, and a woman in her mid 60s with RAS wild-type, BRAF V600E-mutated, MSS mCRC, now receiving encorafenib/cetuximab after disease progression on FOLFOX/bevacizumab — Farshid Dayyani, MD, PhD, and Dr Azzi (59:05) CME information and select publications

A Landmark of OncoPharm from 2004: FOLFIRI --> FOLFOX or FOLFOX --> FOLFIRI. Some interesting dosing to discuss in this study. Link: https://pubmed.ncbi.nlm.nih.gov/?term=37379692

Dr. Shaalan Beg and Dr. Mohamed Salem discuss novel therapies in gastrointestinal cancers, including CAR T therapy and the CodeBreak-101 trial in mCRC, new advances in uHCC in the HIMALAYA trial, and an exciting update from the NAPOLI-3 trial in pancreatic cancer, ahead of the 2023 ASCO Annual Meeting.  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 Simmons Comprehensive Cancer Center. My guest today is Dr. Mohamed Salem, a GI oncologist at the Levine Cancer Institute at Atrium Health. We'll be discussing key posters and oral abstracts in GI oncology that will be featured at the 2023 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode, and disclosures of all guests on the podcast can be found in our transcripts at asco.org/DNpod. Mohamed, thanks for coming on the podcast today.  Dr. Mohamed Salem: Thanks, Shaalan.  Dr. Shaalan Beg: There's some interesting studies in colorectal cancer that I'd like to get us started with today. Abstract 3547 is titled “A Phase I Dose-escalation Study of GCC19 CAR T: A Novel Coupled CAR Therapy for Patients with Metastatic Colorectal Cancer.” What are your thoughts on the study? Dr. Mohamed Salem: Actually, this was a very exciting study to see coming out in GI cancer, especially colorectal cancer. As you know, CAR T made its way to the treatment of lymphoma and other heme malignancies. In fact, we saw a fascinating response and outcome using that technique and that niche in the immunotherapy module. The challenge we had was that we could not replicate this in solid tumors until very recently. I'm sure you had the same thing in your clinic, too. A lot of patients with GI cancer or colorectal cancer come to you and say, "Okay, why can't I have CAR T?" And the response was, "We don't know if it's effective or if it's going to work yet." Here at our center, we had a phase 1 study, I think that was looking also at CAR T and solid tumors, particularly prostate cancer. So that I think was very exciting to see that technology is making its way to the solid tumor. I was very pleased to see this CAR T study coming out from the work of our Chinese colleagues looking into this in the CRC space.  Obviously, as you know, in colorectal cancer, we made a significant advancement, but I don't think we made enough advancement yet, and especially for refractory patients, patients with refractory disease who have underwent multiple lines of therapy. And this study actually addressed the need for those patients. So in this study, that was a phase I escalation dose, very much is we looked at about 13 patients who had metastatic CRC, they had at least two lines of therapy. So in what we say is a "refractory setting," unfortunately for those patients, we don't have large treatment options. And they used two doses, the first dose and the second dose that was a little bit higher. And the interesting part is that they were able to see very nice responses on this patient population. In the lower dose, I think the response was the PFS was about 1.9 months. But when they went up on the dose, actually the PFS was 6.3 months, which I think in the refractory setting is very meaningful.   And also the median overall survival for the first group was 13 months, which in the refractory setting is something we don't see often, and the higher dose was 18 months, which was even better. So there was a trend that higher doses are perhaps more effective or have better efficacies than lower doses, but also in terms of side effects, actually patients were relatively able to tolerate it well, and there were no surprising adverse events. So again, yes, that's 13 patients in total. So it's a very small study, but like everything else, the proof of concept sometimes is the first step and it's very important to see that data to suggest that this technology now can be utilized in solid tumors and CRC, especially now there is an unmet need for those patient populations. I'm sure you and I will see a lot of patients at the clinic with good progress status, and just looking for the next option, and I'm glad to see that. Hopefully, we can continue to build on that work.  Dr. Shaalan Beg: Another key abstract in colorectal cancer is Abstract 3513, the CodeBreak 101 study. This is a phase 1b safety efficacy trial of sotorasib plus panitumumab and chemotherapy with FOLFIRI for previously treated KRAS-G12C mutated colorectal cancer. And this is a really important study because even though KRAS-G12C represents a minority of KRAS mutated colorectal cancer, we know that this treatment can cause meaningful improvement in disease for other cancers like non-small cell lung cancer. And when sotorasib was tested as monotherapy in colorectal cancer, it saw an objective response rate of 9.7% that increased to 30% when added to panitumumab.   So in this trial, they took sotorasib plus panitumumab and added it to chemotherapy to see how it's tolerated and what its effectiveness is going to look like. And they enrolled people who had more than one or more lines of prior therapy for metastatic disease. They treated 33 patients. The most common side effect was dermatologic, which is probably related to EGFR-based therapy, and they saw a confirmed overall response rate of 58%. Side effects are those that we look to expect with this specific regimen. I don't see any additional safety concerns here, but this can be a big step forward for KRAS-G12C-altered colorectal cancer. What do you think? Dr. Mohamed Salem: I totally agree. And again, it was very exciting to see that abstract and that result. I totally believe now, and I'm sure you would agree with me too, Shaalan, that we're moving from an era of one size fits all to a precision oncology and tailored treatment. And the fact now we have a treatment option for patients with a KRAS mutation is very exciting because before, we didn't have much that we can do about that mutation. So now it's not just a proof of concept. Now you're hitting that target with the chemotherapy and you're getting a 50% response rate. That's something interesting also to see for this patient population and as you highlighted as safety also, and the adverse event was not high and patients were able to tolerate it, which makes it more doable for us to use it. Dr. Shaalan Beg: Yeah. And one of the challenges in the precision oncology space, which I'm sure you're experiencing in clinic as well, are the real-world applications of precision oncology and the drop-offs that happen that are preventing us from universal precision oncology - meaning the drop-offs that we see on eligible patients receiving the appropriate genomic testing, those who have genomic testing receiving the appropriate treatment. And we've seen a couple of fairly high-profile studies that are describing this in non-small cell lung cancer where the rates are not as encouraging as we would want it to be, which to me, as a physician, makes me worried that there are people out there who we don't know are carrying these mutations or have these mutations, and it hasn't been acted upon.   And related to that, there is an abstract at ASCO23, which is Abstract 3602, that looked at the real-world rates of FDA-approved targeted therapy and immunotherapy for people with metastatic colorectal cancer. They used the VA's National Precision Oncology Program data to study the prevalence of these mutations and how many of the folks ended up receiving the treatment that would be appropriate for those mutations. And this is a very exciting study. They looked at 908 metastatic colorectal cancer patients who underwent genomic profiling, 81% were colon and the rest were rectal. They found that 34% of patients harbored NRAS, KRAS, BRAF mutations, 9.6% were TMB-high, 7.7% had BRAF V600E, and 5.6% were MSI-high, which kind of puts the overall actionable variant prevalence in colon cancer at 47% and for rectal cancer at 44%.  And then they went down to see amongst those 424 eligible patients, how many ended up on appropriate therapy. And these were their numbers: for MSI-high 70%, TMB-high 47%, NRAS, KRAS, BRAF, wild-type 38%, BRAF V600E 17%. So nearly 30% of patients with MSI-high colorectal cancer did not receive immune checkpoint inhibitor therapy, and again, other aspects in terms of EGFR use, and I know that there are other challenges that may affect the use of EGFR inhibitors in colorectal cancer, but it really begs the point on aspects related to implementation science, on getting the testing and acting on those results. And I'm curious to what you're seeing that's being done on these initiatives nationally.  Dr. Mohamed Salem: I totally agree with you, Shaalan. This is a big problem we're facing day in and day out because we struggle to find treatment options for our patients. And I think if we're missing patient with targetable or actionable mutations and we're not utilizing that, I don't think that's a good situation to be in. And I think that's just a group effort. You have to work with the pathologist, you have to work with your team at the clinic. And as an oncologist treating this patient, we have to pay close attention to those markers. And frankly, just look for them. At least  the ones that you know are going to have therapeutic implications.  I do also think patient advocacy has a huge role here and huge opportunities that they can contribute. I am sure you are familiar with the pancreatic study that was published by our colleague Mike Pishvaian in Lancet a year or two ago. I think he named it the Know Your Tumor Type. I think that should be the way forward now, not just for pancreatic but for any cancer. Patients should ask their oncologists what my tumor is. Is it MSI-high, is it KRAS-G12C, is it BRAF? Because it will affect the treatment. I think it's multi-layer and all of us should work in a cohesive manner to be able to not ever miss those markers which carry therapeutic potential.   Dr. Shaalan Beg: So moving on to hepatocellular carcinoma, Dr. George Lau and colleagues, they'll be sharing data from the phase 3 HIMALAYA study with hepatocellular carcinoma in the Annual Meeting that's Abstract 4004. And he looked at outcomes by occurrence of immune-related events for people who received tremelimumab and durvalumab. What are your thoughts on this study?  Dr. Mohamed Salem: This was a very interesting abstract to see. For a long time, we didn't have many treatment options in hepatocellular carcinoma. So, over the last two or three years now, I think we've made nice advancements in the therapeutic landscape. So, we have multiple options including immunotherapy which is very exciting for all of us to be able to utilize those powerful drugs in that disease. The question that comes out is who actually responds? Obviously, in HCC you don't have a lot of biomarkers like the immune therapy biomarkers like MSI-high and PDL-1, and TMB. It isn't really playing a huge role in HCC. So, as you know, the HIMALAYA study is a phase 3 study and examined the STRIDE regimen which is treme plus durva in the first line of patients with metastatic or unresectable HCC against sorafenib. And the outcome was in favor of the STRIDE regimen with improvement in OS response rate and duration of response and because of that, it became one of the standards of care for that disease. But Abstract 4004 is actually asking a very interesting question - whether immune-related adverse events can predict outcomes. Meaning like those patients who experience immune-related adverse events will likely do better compared to those patients who didn't experience immune-related adverse events or not. The idea of adverse events as a biomarker if you will, for efficacy is not new. I mean we saw that back in the renal carcinoma TKI, hypertension. People who had hypertension were more likely to have a better response. In the GI also there was some data suggesting that rash might be a biomarker in predicting response to EGFR. So the same question we're applying here - immune-related adverse events can function as a biomarker for efficacy for the immune system.  And there are some data out there in other tumors that may be the case, but I think at least to my knowledge in the HCC or GI, this was the first study to address that question. So just to remind our audience that the HIMALAYA was a phase 3 study using the STRIDE regimen as a frontline for patients with hepatocellular carcinoma, either unresectable or metastatic disease. And they compared the STRIDE which is durva-treme compared to the standard of care at that time was sorafenib. The primary endpoint was overall survival and they had secondary endpoint duration of response, response rate, and obviously adverse event.  The study was positive, it met its primary endpoint and OS was in favor of the STRIDE regimen compared to sorafenib. But that part of the abstract now is focusing mainly on those patients who had immune therapy and whether that was a STRIDE regimen or the third arm that durva alone treatment. And they're looking at those patients who had immune-related adverse events, and those who didn't have immune-related adverse events. So basically four groups of patients, the patient who had a STRIDE regimen, about 139 patients had immune-related adverse events, and about 249 didn't have immune-related adverse events. For the cohort who had durva alone, about 64 patients had immune-related adverse events, almost 300 patients had no immune-related adverse events.  And it was very interesting that at least in the STRIDE arm, those patients who experienced immune-related adverse events, their outcome was better than those patients who did not have immune-related adverse events. It's the same trend seen on the durva alone arm, but I think the number was very small to make a statistical value out of it. But I think at least in the STRIDE arm there was a suggestive trend toward the outcome of those patients who experienced immune-related adverse events. So I think this is in a way very interesting because we're always wondering if we give the same dose at least in immunotherapy like for everyone.   What I was wondering is if it's too much, too little, or just right. It's hard to know for sure. But perhaps in my opinion and just me trying to understand why, in my theory, maybe that's just an indication of patients receiving enough drugs and effective drugs that will translate into efficacy. But at the same time, I also wanted to just put a word of caution here because we don't want to see side effects as a good thing. I think we want to make sure that us as oncologists treating these patients and patients also don't see like it's good to have a side effect. Side effects associated with especially those grade 3 or 4 can be associated with significant problems and decreased quality of life. So, definitely should be looking at those side effects and be careful interpreting those data. But I think that is very interesting and I will look for more work on that.   Dr. Shaalan Beg: Let's move on to pancreatic cancer. We heard the results of the NAPOLI-3 clinical trial at GI ASCO and this year in ASCO 2023 we will hear the results of Abstract 4006 by Dr. O'Reilly that are presenting results of the 12 and 18-month survival rates from the study that compared NALIRIFOX or nano-liposomal irinotecan, 5-fluoro/leucovorin, and oxaliplatin versus nab-paclitaxel/gemcitabine for newly diagnosed pancreatic cancer patients. I'm interested to hear what you think about that study. Dr. Mohamed Salem: Thank you, Shaalan. So this also is a very exciting abstract to see, and anyone who treats pancreatic cancer patients realizes that, unfortunately, even in 2023, we don't have a lot of treatment options. And yes, I think over the last decade we're now talking about second-line and third-line, but yet we still don't have a lot of treatment options. So, having more options is always good. But the question now is how do you sequence those chemotherapy options? Most of us obviously use FOLFIRINOX in the first line or gemcitabine and paclitaxel in the first line. Until very recently– because we didn't have a head-to-head comparison– we couldn't tell patients for sure if one is better than the other. I think we had some assumptions, but it wasn't really proven. It was just a cross-trial comparison.  So, the fact is that now we have that phase 3 trial looking at liposomal irinotecan, 5-fluoro/leucovorin and the oxaliplatin comparing to nab-paclitaxel/gemcitabine. To me, that was actually very exciting because now, at least, I can see a triplet chemotherapy drug compared to a doublet chemotherapy drug. And as you mentioned, Shaalan, the first initial read was positive in favor of the triplet regimen compared to the doublet, which I think was an important message to give to our colleagues and all of us that if you can, obviously, the triplet comes with side effects, but if you can deliver the triplet, that's perhaps a better starting point for the treatment. But the study here, we're trying to get more read after more mature or more time-lapsing. So the initial study was initial read was positive. And I think this is good to see, too because it translates that even with a longer follow-up, we're still seeing the same benefit. So the OS rate in 12 months for the triplet was about 45% compared to 39.5% for the doublet, and the 18 months, a year and a half, was 26% compared to 19%. So, definitely, you can see an improvement in every single endpoint. OS in general was 11.1 months compared to 9.2 months, and PFS was also in favor of the triplet. So I think it's a message here to reinforce what we saw a few months ago in the initial presentation that, in fact, the triplet is associated with better outcomes if you can safely manage the toxicity and guide the patient through the process. Dr. Shaalan Beg: Well, thank you very much, Mohamed. This was a lot of fun. Thanks for sharing your valuable insights with us on the ASCO Daily News Podcast. Dr. Mohamed Salem: Thank you for having me and looking forward to the full presentation at the meeting. And please, if you haven't registered for the meeting yet, make sure you attend. It's a wonderful opportunity to learn from an expert in the field and also meet your colleagues and make new friends. I also want to take this opportunity to thank the ASCO Daily News Podcast team for taking the time, and also for our colleagues who reviewed these abstracts. This takes a lot of time and effort, and I think they're doing a wonderful job. So, thank you to all of them, and I'll see you all at ASCO.  Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcript 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 us for more key insights from ASCO 23 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 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, 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. 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

Featuring perspectives from Drs Tanios Bekaii-Saab, Scott Kopetz, and John Strickler and Prof Eric Van Cutsem, moderated by Dr Kristen Ciombor, including the following topics: •      Integration of Therapies Targeting BRAF and HER2 in Metastatic Colorectal Cancer (mCRC) — Dr Strickler o   Introduction (0:00) o   Case: A man in his early 40s presenting with microsatellite-stable (MSS) rectal cancer and liver metastases — Victoria Giffi, MD (2:04) o   Cases: A man in his late 70s with HER2-amplified colon cancer and extensive liver metastases and a man in his late 50s with KRAS G12S-mutant HER2-amplified colon cancer and lung metastases — Ranju Gupta, MD and Shaachi Gupta, MD, MPH (9:12) o   Faculty presentation (16:39) •      Optimizing the Use of Immune Checkpoint Inhibitors in the Management of mCRC — Dr Ciombor o   Case: A man in his mid 50s with BRAF V600E-mutant, KRAS/NRAS wild-type metastatic colon cancer with disease progression on FOLFOXIRI/bevacizumab — Lai (Amber) Xu, MD, PhD (26:13) o   Case: A man in his late 60s with localized unresectable microsatellite instability-high carcinoma of the cecum — Farshid Dayyani, MD, PhD (32:02) o   Faculty presentation (41:11) •      Evidence-Based Selection and Sequencing of Therapy for Patients with mCRC — Prof Van Cutsem o   Case: A man in his late 70s with metastatic rectal cancer and newly diagnosed PMS2-positive Lynch syndrome — Liudmila N Schafer, MD (51:39) o   Case: A man in his mid 50s with pan-RAS wild-type metastatic rectal cancer treated with FOLFOX/cetuximab — Warren S Brenner, MD (56:55) o   Faculty presentation (1:03:36) •      Promising Agents and Strategies for Patients with mCRC — Dr Bekaii-Saab o   Case: A woman in her early 50s with KRAS and BRAF wild-type, HER2-negative T3N1 rectal cancer with liver and lung oligometastases who underwent multiple ablations and stereotactic body radiation therapy and is currently receiving FOLFIRI/panitumumab – MSS, mismatch repair-proficient, PD-L1 0% — Jennifer L Dallas, MD (1:13:13) o   Case: A woman in her early 60s with metastatic KRAS G12C-mutant cancer of the sigmoid colon — Philip L Brooks, MD (1:18:43) o   Faculty presentation (1:22:32) •      The Changing Management Paradigm for Localized CRC — Dr Kopetz o   Case: A man in his early 70s with 2 synchronous T3N0 cancers of the splenic flexure and cecum who is found to have circulating tumor DNA after resection — Dr Brenner (1:35:56) o   Case: A man in his early 80s with a Stage II obstructing cancer of the right colon — Namrata I Peswani, MD (1:46:12) o   Faculty presentation (1:47:58) CME information and select publications

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, Cancer.Net Editorial Board members discuss new research in gastrointestinal and genitourinary cancers presented at this year's ESMO Congress, held September 9-13 in Paris, France. First, Dr. David Ilson discusses treatment advances in liver, colorectal, and gastric, or stomach, cancers. Dr. Ilson is an attending physician and member at Memorial Sloan Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College. You can view Dr. Ilson's disclosures at Cancer.Net. Dr. Ilson: Hi, I'm Dr. David Ilson from Memorial Sloan Kettering Cancer Center in New York. I'm a GI medical oncologist, and it's my pleasure today to review some important presentations in GI cancers from the recent ESMO meeting in Paris from 2022. I have no relevant relationships to disclose for this discussion. So, important presentations were made in hepatocellular cancer, in colorectal cancer, and gastric and other cancers, and I'm going to highlight some of the key presentations from the meeting.  One of the most anxiously awaited presentations was one in hepatocellular or liver cancer. For patients that have advanced disease who are not candidates for surgery or local treatments, standard therapy now, it used to be lenvatinib and sorafenib, and that's now been replaced by the combination of an immunotherapy drug, atezolizumab combined with the drug bevacizumab. That's the new standard of care. And recently, we had a promising data for another immunotherapy combination using the drug durvalumab combined with tremelimumab. So what we saw this year was another important global study looking at the first-line use of immunotherapy in hepatocellular cancer. This trial took 794 patients with advanced hepatocellular cancer and assigned them to a standard treatment with a drug called lenvatinib. Lenvatinib and sorafenib were the old standard treatments for hepatocellular cancer. And lenvatinib alone was compared to a combination of lenvatinib and pembrolizumab, an immunotherapy drug. The primary endpoint was to see whether adding immunotherapy to lenvatinib improved survival. And this was a negative trial. It did not show an improvement in survival for adding pembrolizumab to lenvatinib over lenvatinib alone, and there was really no significant difference in the time that patients were on treatment. The response was slightly higher with the addition of pembrolizumab to lenvatinib, but again there was no survival difference. So this combination will not move forward. And again, as I said earlier, the new standard first-line treatment is atezolizumab plus bevacizumab. In colorectal cancer, probably one of the most exciting presentations was the use of immunotherapy treatments in locally advanced colon cancer. There is an important subset of colorectal cancer that has what's called an MSI-high status. MSI-high colon cancers are very responsive to immunotherapy drugs, and there has been a lot of interest in patients with localized colorectal cancer using immunotherapy drugs prior to surgery rather than conventional chemotherapy or radiation. So this important trial looked at 112 patients with localized colorectal cancer. Most of the patients were stage 3, and they all were documented to have this MSI-high status, which indicated a higher chance of response to immunotherapy. And patients received a brief course of immunotherapy, 2 doses of the drug nivolumab combined with 1 dose of ipilimumab over only 6 weeks followed by surgery. What they showed in these 112 patients who went to surgery, there was almost 100% response to this treatment. In fact, almost two-thirds of patients had no cancer found at surgery, even only after several weeks of immunotherapy. And in the 112 patients treated, there have been no recurrences in any of these patients. So it's quite remarkable that immunotherapy could induce a complete remission in two-thirds of patients, and that was only after a few weeks of exposure of the drug. So I think we're going to see more interest in using immunotherapy treatments as a potential pre-surgical treatment for colon cancer. And we could argue with such a high rate of complete remission, if we gave immunotherapy longer, maybe we could consider nonsurgical management, to just keep treating the patients with immunotherapy. This is actually the case that's now been seen in rectal cancer, a recent study presented from my institution where they treated patients with rectal cancer with immunotherapy, and we also achieved 100% remission, and none of the patients in this small study required surgery. So I think this important study, which is called the NICHE-2 trial, indicates a high degree of effectiveness of immunotherapy in MSI-high colon cancers. And certainly, it raises interest in using this as a preoperative treatment and potentially could lead to some patients getting treatment with immunotherapy alone without surgery. Then I'm going to comment a little bit about advanced metastatic colon cancer. Another important presentation was studying a new drug called fruquintinib. Fruquintinib is an oral drug that targets the VEGF pathway, which is an angiogenesis pathway in colon cancer. Standard treatment for colon cancer when it's stage 4 disease is now use of chemotherapy, like FOLFOX and FOLFIRI, drugs like bevacizumab, cetuximab, and panitumumab. And in more chemotherapy-resistant cancers, we use drugs like regorafenib and TAS-102. So this trial looked at a large group of patients, over 690 patients who had received all conventional treatments. They had progressive disease on all conventional treatments, including the late-line drugs regorafenib and TAS-102. And this was a placebo-controlled trial in which patients either received the drug fruquintinib or they received placebo plus supportive care. It was reasonable to offer a placebo in this trial because there really was no other standard treatment option for these patients. The primary endpoint of overall survival was improved with fruquintinib. Survival was improved with a reduction in the risk of death by about 30% and improvement in time on treatment. Very few patients responded to fruquintinib, so this was largely a drug that stabilized the cancer, but it did lead to modest improvements in time on treatment and modest improvements in survival. So this drug may potentially be evaluated as a new treatment option in very chemotherapy-resistant colorectal cancer. I just want to mention briefly another new class of agents for which we had data presented at the ESMO meeting. These are drugs that inhibit a mutation in their cancer called KRAS G12C. There are promising drugs that target this pathway. And there were 2 drugs that were followed up on at ESMO, one was a drug called sotorasib and another drug was adagrasib. These are drugs that target KRAS G12C mutations in colon cancer. And both of the trials that were presented used these drugs combined with drugs that target the EGFR pathways, so either panitumumab or cetuximab, and very encouraging responses were seen on these trials. The trial that looked at the combination of adagrasib plus cetuximab achieved a response in about 46% of patients, which is very encouraging. The trial that studied sotorasib, combined sotorasib with panitumumab, and they observed a 30% response, and some of these responses were durable. So the take-home message is that these drugs, adagrasib and sotorasib, are promising new agents to target KRAS G12C mutations in patients with advanced colon cancer and indicate that we may get even a higher degree of activity when we add EGFR-targeted drugs including panitumumab or cetuximab to these agents. So the other area that I want to comment on is gastric cancer. Recently, in the United States, we had a regulatory approval for the drug trastuzumab deruxtecan in patients who have HER2-positive gastric cancer that's advanced and is being treated with chemotherapy alone, HER-2-positive patients who had received previous trastuzumab or Herceptin. So trastuzumab deruxtecan is a promising drug used in patients that develop resistance to trastuzumab. So there was an update of the trial called Gastric-DESTINY02, which was a phase 2 trial of trastuzumab deruxtecan in Wwestern patients as a second-line treatment for patients with HER2-positive gastric cancer, and the updated analysis again showed a promising response in 40% of patients. The response duration was about 8 months, and patients achieved a survival of a year or more. So this updated presentation really reinforced that this is an active drug for patients with HER2-positive gastric cancer whose disease progresses on previous treatment with trastuzumab. So this was a very exciting ESMO meeting. There were a lot of other studies and important presentations, but I've tried to highlight today what I think are the most important as we move forward in trying to identify new treatments for patients. ASCO: Thank you, Dr. Ilson. Next, Dr. Sumanta (Monty) Pal and Dr. Tian Zhang discuss new research in kidney, bladder, and prostate cancers. Dr. Pal is the co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and is a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. You can view disclosures for Dr. Pal and Dr. Zhang at Cancer.Net. Dr. Pal: Welcome to this Cancer.Net podcast. My name is Monty Pal. I'm a medical oncologist in the City of Hope in Los Angeles. I'm thrilled to be here today with my dear friend and colleague, Dr. Tian Zhang from UT Southwestern. Tian, mind giving us a quick intro? Dr. Zhang: Hi, Monty. Great to be here with you today. Tian Zhang at UT Southwestern in Dallas, Texas, where I'm a GU medical oncologist. I'm really excited to talk through the ESMO trials with you today. Dr. Pal: A little bit of housekeeping first. Let's go ahead and get some of our disclosures out of the way. I get travel support from CRISPR Therapeutics and from Ipsen. Tian, how about you? Dr. Zhang: Sure. I've received honoraria from Exelixis, BMS, Genentech, AstraZeneca, and Janssen, all relevant to our discussion today. Dr. Pal: Very good, very good. Well, thank you so much for joining us today. We've got a lot to talk about in about 15 minutes. The first thing that I wanted to chat about is adjuvant therapy. First of all, before we dive into the weeds here, can you just kind of tell our audience what adjuvant therapy is in broad strokes? Dr. Zhang: In kidney cancer, we think a lot about how we might prevent disease recurrence after surgery. So adjuvant treatment refers to systemic treatment that's given after a big surgery. And so in kidney cancer, that's usually after nephrectomy or removal of the kidney. Dr. Pal: Excellent, excellent. You beat me to the punchline. We are going to focus on kidney cancer, no doubt. This year at the European Society of Medical Oncology, or ESMO, meeting, which was held in early September, we actually had some really key studies presented in this space, one of which I'll disclose that I led. Studies I would say were maybe a little bit disheartening there, but nonetheless, I do think we can learn a lot from them. One of these trials was called PROSPER. This was a really interesting study that actually didn't just look at adjuvant therapy but actually looked at treatment before surgery, which we called neoadjuvant therapy. Tian, can you kind of walk us through the design of that trial really quickly? Dr. Zhang: This was a trial done in the ECOG Cooperative Group, and patients were randomized to receiving either nivolumab, which is an immune checkpoint inhibitor, before surgery, followed by a year of nivolumab after surgery, or to surgery and observation with ongoing scans. So it was really trying to look at a perioperative approach of using nivolumab. Dr. Pal: So how about this? Maybe we'll kind of discuss some of these results in amalgam, but maybe let's go through these trial designs first. The second trial that was highlighted this year at ESMO was called IMmotion010. That's one thing that I just love about these studies. They all have very clever names. I don't know what an IMmotion is, but tell us about IMmotion010 and what that trial design looked like. Dr. Zhang: Sure. So IMmotion010, again, also was an adjuvant trial for resected intermediate- and high-risk kidney cancers, randomized folks to either atezolizumab for a year or placebo for a year. And so this is in the context of having had resected kidney cancers and following folks for the treatment results, and the primary endpoint there was disease-free survival. Dr. Pal: Okay. So we've got an immune therapy called nivolumab and the PROSPER trial that was looked at before and after surgery. We've got atezolizumab, a different checkpoint inhibitor that was looked at following surgery. Tell us about the third trial. This is the last study in the space called CheckMate 914. What did that trial look at? Dr. Zhang: That one, again, also a phase 3 adjuvant trial, enrolling folks after surgery that had high-risk kidney cancer and randomized to either the combination of nivolumab with ipilimumab, both checkpoint inhibitors versus placebo. And again, this treated patients for about 6 months and also primary endpoint of disease-free survival. Dr. Pal: Now, whenever we do these studies, we always define them as being positive or negative, and that's really not meant to sort of cast any aspersions on how well the study was done or any really sentiments around the trial itself. It's really objective, and it's based on whether or not a study hits what we define ahead of the trial as being called a primary endpoint. So we actually, in these studies, looked at a primary endpoint of something called recurrence-free survival. And so that's really the proportion of patients who actually are living on without any sort of recurrence of their kidney cancer. I think it might be easy enough to sort of describe whether or not these trials hit that endpoint were positive or negative. What was the final report here on these trials, Tian? Dr. Zhang: Well, Monty, I think all 3 of these trials were, quote-unquote, "negative," and we all had high hopes for all 3 of these trials. And certainly, many, many patients participated, and we will learn eventually a lot from these trials. But none of these 3 met their prespecified primary endpoint of recurrence-free survival endpoint. Dr. Pal: So this is a little bit tricky because we did have these 3 negative studies presented at ESMO this year, but there was 1 positive trial that's adjuvant or postoperative space presented previously and then now published, actually, in the New England Journal of Medicine with an FDA approval to boot. Can you tell us about that, Tian? Dr. Zhang: Well, that one was called KEYNOTE-564 and randomized patients to either a year of pembrolizumab or placebo. And so you're absolutely right. It did show an improvement in disease-free survival comparing pembrolizumab with placebo. And so pembrolizumab is approved in this adjuvant setting after nephrectomy. Dr. Pal: And so this can be kind of a tough space because I can imagine our listeners are hearing this saying, "OK. Well, at ESMO, we've got 3 negative trials looking at postoperative therapy, and we've got 1 positive trial looking at pembrolizumab in the space." So what's one to do in this setting? What are you telling patients these days about whether or not to use adjuvant treatment for kidney cancer? Dr. Zhang: Yeah. I think it's a conversation that patients have with their oncologist after surgery, and it really depends on their own risk factors, their clinical and pathologic features at the time of resection. It depends a lot on patient preferences and their own priorities and things such as their tolerance for toxicity or how often they're coming into the treatment center. And I do think this is a time point where they have a shared decision-making that we can help our patients understand the totality of the data and then decide if a year of pembrolizumab is worthwhile or if they'd rather continue with surveillance after surgery. Dr. Pal: I totally agree with you, and I love that term “shared decision-making,” because it's never one of those situations where I walk into the clinic room and say, "Here's what you're going to do." And it's also never the situation where the patient walks into the clinic room and says, "Here's what I want." It's always this really sort of mutual process, isn't it, where you sort of look at a patient's clinical state. You look at some of the features under the microscope, but then it comes down to really, really lengthy and personal discussions around what that patient wants to get out of treatment. So I think that's very well said, Tian.  I'm going to move to actually a different setting, which is termed “metastatic disease.” So we've talked about localized kidney cancer, where the disease is sort of confined to the kidney for the most part. We talked about what we do after we remove visible evidence of disease. But there is, unfortunately, a number of patients where we can't necessarily remove all the disease burden. So we lean more heavily on what we call systemic treatments. These are treatments that enter into the bloodstream either by mouth or through the veins. And in kidney cancer, just to give you a really, really brief synopsis, there's been this huge evolution over time. When I started in the field, it was really the advent of using a single oral therapy for kidney cancer. And over the next five 5 years, we sort of saw this evolution towards using doublet therapies, which is a mix of pills and IVs or maybe IVs alone. And more recently, there's been a lot of excitement. You can probably see where this is going, right? We've looked at 1 drug, and it works. We've looked at 2 drugs, and they seem to work. Logic would perhaps suggest that maybe you could get away with using 3 drugs in concert. So, Tian, this year at ESMO, there was a really important trial called COSMIC-313 that looked at 3 drugs versus 2 drugs. Can you tell us a little bit more about the design of the study? Dr. Zhang: COSMIC-313, the large phase 3 study, which randomized more than 850 patients to either the triplet, as you're speaking of, the cabozantinib, nivolumab, and ipilimumab versus nivolumab and ipilimumab with placebo standing in for cabozantinib. And so this was a very large trial, looking particularly at progression-free survival, comparing the triplet versus the immunotherapy doublet. Dr. Pal: And then tell us about the results of this because I have to tell you. I mean, I spent a lot of time looking over this, and I struggled with the end results a little bit. We talked about the primary endpoint of studies when we were discussing adjuvant therapy. And one of the things we'd mentioned is that you decide on this beforehand. And the primary endpoint in this trial was actually the delay in cancer growth. And as you pointed out, the study met that endpoint. But how do you interpret the results overall? How are you incorporating triplet therapy now? Dr. Zhang: Sure. I think it did certainly meet the progression-free survival primary endpoint. The median was not reached for the triplet versus 11.3 months for the doublet. And so importantly, I think it was a, quote-unquote, "positive trial." But how are we using this? Well, we have not seen the overall survival data of these patients. And so when you're thinking about combining all 3 drugs in the frontline setting, I think it's really important to think about what might come after and whether these folks truly live longer with using all 3 upfront versus a sequential approach. So I think the jury is still out. It certainly met its primary endpoint, and it's quite promising. But I'm still waiting for the overall survival data to really inform or change my practice. Dr. Pal: I've got to agree with you there. One of the things that we always discussed in clinic is whether or not a particular treatment strategy is going to increase longevity. It comes up in every conversation, I would say, whenever we're thinking about approaching a new line of treatment. And I wish I could say definitively that this triplet strategy improves longevity, but to be totally fair, that data just doesn't exist yet. So it's a really difficult conversation. I agree with you. Maybe a little pause before we start incorporating triplets. So I've got to say, it was certainly a big year for kidney cancer, one of my fellows put this table together, and it really showed that this year amongst the past maybe 10 years in kidney cancer, we had more big phase 3 trials being reported as more than any year previously. But there are also some pretty key developments in other diseases that you and I treat, Tian, and one of those is bladder cancer. And a trial that I think was really quite important has the name EV-103. Tough name to remember, but it actually looked at a disease space that I think can be a bit of a challenge for us, and that's the patient who is presenting in the clinic has actually advanced bladder cancers spread to other parts of the body and is quite ill and perhaps can't receive conventional aggressive chemotherapy with a drug called cisplatin. So what did this proportion of EV-103 that was presented show us? Dr. Zhang: Well, people hear about Cohort K thrown around, and so this trial actually has had multiple cohorts. And this particular cohort came out of some really exciting data from their dose escalation studies, and also Cohort A, where patients were treated with an antibody drug conjugate, this enfortumab vedotin, or EV, with an immune checkpoint inhibitor called pembrolizumab. And in the early cohort of 40 patients, they saw a pretty high objective response rate. That means the rate of patients where tumors were shrinking. And so that was about 70% of those 40 patients had objective responses. And so they designed this Cohort K to randomize patients to either enfortumab vedotin with pembrolizumab or enfortumab vedotin on its own, which has been approved in refractory metastatic urothelial cancer but particularly for first-line cisplatin-ineligible patient population. And so they randomized about 150 patients in the setting and looked at objective responses, and I agree with you. Certainly, very promising in terms of having objective response rate of about 65% and compared with enfortumab vedotin on its own, which came in around 45%. It does seem that this combination has more activity than the monotherapy. Dr. Pal: Yeah. That's a great summary. And to the patients out there listening, when we talk about responses, we're talking about pretty deep responses here, meaning 30% or more reductions in the size of tumors. And Tian mentions that you've got 65% to 70% of patients with these responses. It really does entail a sizable reduction, not just a small decrease in the volume of tumors. And I'm telling you, just from having been in the scene for 15 years now, I mean, it's just remarkable sort of progress that we're making.  We're going to wrap up by talking about prostate cancer, and just to really describe some overarching results. So there's a setting in prostate cancer that I always find to be a bit of a challenge, and these are patients who have had surgery for their prostate cancer. So extensively no visible spread of their disease, but they start having their PSA creep up afterwards. And there was a trial that sort of addressed that. Tian, can you give us the sort of quick and dirty summary of the study? Dr. Zhang: Sure. So we call this PSA recurrence or biochemical recurrence setting. And this trial was led by Dr. Rahul Aggarwal in the Alliance Cooperative Group. But everyone who had biochemical recurrence were randomized to receiving androgen deprivation therapy alone, which is usually our standard of care; a combination of that androgen deprivation therapy with apalutamide, which is an androgen receptor blocker; or the combination of a triplet of the androgen deprivation therapy, the apalutamide, and then an abiraterone acetate, which is a blocker of steroid synthesis in the adrenal glands. And so this trial enrolled ultimately about 500 patients and randomized them 1 to 1 to 1 to these 3 cohorts. And interestingly, the combinations of either the androgen receptor, androgen deprivation therapy with apalutamide or the triplet with combined abiraterone acetate all prolonged PSA progression-free survival compared to androgen deprivation therapy alone. So I think it was a really well-done study in the cooperative groups and helps answer some questions around intensifying treatment in that biochemical recurrent space. Dr. Pal: Yeah. These cooperative groups studies, each one of them are so critical. These are just funded by our federal government, and they really offer us a chance to really ask pure questions, so really, really important study design. And maybe in 30 seconds, let's go over this last study over here. I don't want to keep our listeners on for too long, but there was a study called PROpel. Again, you got to love these study names. So this PROpel study looked at advanced prostate cancer. So again, this is prostate cancer where the disease has spread from the prostate to other organ systems. This is potentially a new paradigm for the disease. Before, we used to just basically give everybody hormone therapy in this setting. We've doubled down and given patients more advanced hormonal therapy with drugs like abiraterone that you alluded to, but now there's this potential to use targeted treatments. And maybe you can tell us a little bit about how that's been incorporated in PROpel, Tian. Dr. Zhang: Sure. Well, PROpel randomized patients to a combination of abiraterone with olaparib, which is what we call PARP inhibitor, and it blocks DNA damage repair, basically, in cancer cells. And olaparib has been approved as a single agent in more refractory, metastatic, castration-resistant prostate cancer. And so this trial randomized folks with a combination in sort of earlier lines of castration-resistant disease to either that combination or abiraterone with placebo. We saw earlier this year, actually, that the primary endpoint was improved for all comers, but I don't know if we saw some more subgroup analysis of patients with BRCA alterations and also with homologous recombination repair alterations. And I think that's very important, the fact that we saw more of an improvement in those subpopulations than those patients without the BRCA alterations or the homologous recombination repair mutations. Dr. Pal: Excellent. Excellent summary. I think that's about all that we've got time for today. New paradigms in prostate cancer and bladder cancer potentially and a massive amount of new data in kidney cancer to things going forward with clinical practice from ESMO 2022. Tian, thanks so much for joining me today, and I hope everyone listening enjoyed this as well. Dr. Zhang: Thanks, Monty. Take care. ASCO: Thank you, Dr. Pal and Dr. Zhang. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

COR2ED Medical Education: This second GI CONNECT podcast episode, covers the highlights on gastroesophageal cancer from ESMO 2022. Dr Sam Klempner (Massachusetts General Hospital, Boston, USA) and Dr Yelena Janjigian (Memorial Sloan Kettering Cancer Center, New York, USA) discuss a number of key posters and oral presentations from the meeting and their implications for clinical practice. The experts start by covering a number of first line studies. First of all, they discuss a study from Dr. Janjigian’s research group which investigated regorafenib with nivolumab and FOLFOX in HER2 negative oesophagastric cancer. They then discuss LEAP-015 which investigated first-line lenvatinib plus pembrolizumab plus chemotherapy in advanced/metastatic gastroesophageal adenocarcinoma (GEA). Dr. Klempner then covers one of his posters from ESMO 2022 on the DisTinGuish trial which looked at DKN-01 and tislelizumab plus chemotherapy as first-line investigational therapy in GEA. Later they discuss MOONLIGHT which investigated FOLFOX plus nivolumab and ipilimumab versus FOLFOX induction followed by nivolumab and ipilimumab in patients with previously untreated advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Later in the podcast, they cover a number of second line studies, including the PRODIGE 59 - DURIGAST trial which evaluated FOLFIRI plus durvalumab and FOLFIRI plus durvalumab plus tremelimumab in second line treatment of patients with advanced gastric or GEJ adenocarcinoma. Finally they discuss DESTINY-Gastric02 which followed on from DESTINY-Gastric01 in Asian patients and was undertaken to evaluate T-DXd in Western patients with HER2+ unresectable/metastatic gastric/GEJ cancer who progressed on or after trastuzumab-containing regimen.

El Dr. David José Heredia Vázquez, oncólogo médico adscrito al Departamento de Tumores Torácicos del Instituto Nacional de Cancerología, en la Ciudad de México, México, nos comenta en este podcast sobre los highlights del día 4 del Congreso Anual de la Sociedad Americana de Oncología Clínica 2022. Cáncer de ovario: ATHENA-MONO: Estudio fase III, aleatorizado y doble ciego, que evaluó rucaparib en monoterapia vs. placebo como tratamiento de mantenimiento después de la respuesta a la quimioterapia (QT) de 1L basada en platino en pacientes con cáncer de ovario. Cáncer colorrectal: OPTICAL: Estudio fase III, multicéntrico y aleatorizado, que evaluó la QT perioperatoria con mFOLFOX6 o CAPOX vs. el estándar de tratamiento, en pacientes con cáncer de colon localmente avanzado. IMPROVE: Estudio fase II, prospectivo, aleatorizado, no comparativo, abierto y multicéntrico, que evaluó panitumumab intermitente o continuo + FOLFIRI como tratamiento de 1L en pacientes con cáncer colorrectal metastásico, irresecable, sin tratamiento previo, RAS/BRAF w/t. TRIPLETE: Estudio fase III, aleatorizado, de etiqueta abierta, y prospectivo, que evaluó mFOLFOXIRI + panitumumab vs. mFOLFOX6 + panitumumab, como tratamiento inicial en pacientes con cáncer colorrectal metastásico RAS/BRAF w/t no resecable. Sistema Nervioso Central: Alliance A071102: Estudio fase II/III, aleatorizado, que evaluó veliparib o placebo + temozolomida adyuvante en pacientes con glioblastoma recién diagnosticado con hipermetilación del promotor del gen MGMT. Cáncer de pulmón: BTCRC LUN 16-081: Análisis del ADN tumoral circulante del estudio fase II, aleatorizado, que evaluó la consolidación de nivolumab + ipilimumab vs. nivolumab solo, después de QT + radioterapia concurrente en pacientes con cáncer de pulmón de células no pequeñas en estadio III irresecable. Fecha de grabación: 06 de junio de 2022. Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

Description: Metachronous colorectal liver metastasis (CRLM) is a complex clinical situation requiring multidisciplinary management. In this episode from the Hepato-Pancreato-Biliary team at Behind the Knife, we discuss a patient presenting with metachronous CRLM and how management may change with varying clinical scenarios.  Learning Objectives: In this episode, we review the initial workup and pre-operative considerations in a patient presenting with metachronous CRLM.  We discuss key aspects of resectability of CRLM, including physiologic and hepatic fitness, biology of the disease, and technical considerations.  We review the timing and common regimens of systemic treatment for differing clinical scenarios, as well as when adjuncts to treatment may be useful (e.g., portal venous embolization).  Finally, we highlight important aspects of intraoperative and postoperative management. Hosts: Timothy Vreeland, MD, FACS (@vreelant) is an Associate Professor of Surgery at the Uniformed Services University of the Health Sciences and Surgical Oncologist at Brooke Army Medical Center Daniel Nelson, DO, FACS (@usarmydoc24) is an Associate Professor of Surgery at the Uniformed Services University of the Health Sciences and Surgical Oncologist at William Beaumont Army Medical Center Connor Chick, MD (@connor_chick) is a PGY-5 General Surgery resident at Brooke Army Medical Center Lexy (Alexandra) Adams, MD, MPH (@lexyadams16) is a PGY-4 General Surgery resident at Brooke Army Medical Center Beth (Elizabeth) Carpenter, MD (@elizcarpenter16) is a PGY-3 General Surgery resident at Brooke Army Medical Center  Links to Papers Referenced in this Episode: NCCN Guidelines for Colon Cancer https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf Mutation Status of RAS, TP53, and SMAD4 is Superior to Mutation Status of RAS Alone for Predicting Prognosis after Resection of Colorectal Liver Metastases. Clin Cancer Res. 2019 Oct 1;25(19):5843-5851. doi: 10.1158/1078-0432.CCR-19-0863. Epub 2019 Jun 20. PMID: 31221662; PMCID: PMC6774854. https://pubmed.ncbi.nlm.nih.gov/31221662/ Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1208-15. doi: 10.1016/S1470-2045(13)70447-9. Epub 2013 Oct 11. PMID: 24120480. https://pubmed.ncbi.nlm.nih.gov/24120480/ FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015 Oct;16(13):1306-15. doi: 10.1016/S1470-2045(15)00122-9. Epub 2015 Aug 31. PMID: 26338525. https://pubmed.ncbi.nlm.nih.gov/26338525/ Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14. PMID: 30552157; PMCID: PMC6656450. https://pubmed.ncbi.nlm.nih.gov/30552157/ Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015 Apr;26(4):702-708. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23. PMID: 25538173. https://pubmed.ncbi.nlm.nih.gov/25538173/ Recommended Additional Podcasts on CRLM: The AHPBA Podcast: 1.     Episode 1: Dr. Jean Nicolas Vauthey - Colorectal Liver Metastases (https://podcasts.apple.com/us/podcast/episode-1-dr-jean-nicolas-vauthey-colorectal-liver/id1501441845?i=1000467381474) 2.     Episode 12:Dr D'Angelica - Colorectal Liver Metastases and Hepatic Artery Infusion Pumps (https://podcasts.apple.com/us/podcast/episode-12-dr-dangelica-colorectal-liver-metastases/id1501441845?i=1000521718184) Behind the Knife: 1.     Surgical Oncology-Hepatic Artery Infusion Pump (https://podcasts.apple.com/ye/podcast/surgical-oncology-hepatic-artery-infusion-pump/id980990143?i=1000525833877) Please visit behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  

Discussing the Impact of the Pandemic on the Management of Lung, Breast, Gastrointestinal and Genitourinary Cancers — Part 3: Interview with Dr Bekaii-Saab on the following topics: Gastrointestinal cancers in the COVID-19 era (00:00) Case (Dr Bekaii-Saab): A woman in her early 60s with pancreatic neuroendocrine cancer and liver metastases develops COVID-19 (19:41) Case (Dr Bekaii-Saab): A man in his early 70s receiving FOLFIRI/binimetinib for microsatellite stable, RAS/RAF wild-type colon cancer recovers after severe COVID-19 (22:52) Changes in patterns of care for patients with gastrointestinal cancers during the COVID-19 pandemic (26:18) Challenges with the use of chemotherapy and immunotherapy for patients with cancer in the COVID-19 era (37:59) CME information and select publications

Pacientes com câncer colorretal metastático, portadores da mutação BRAF V600E têm um prognóstico muito ruim, com uma mediana de SG em torno de 4 a 6 meses após falha da terapia inicial. Sabendo que a inibição do BRAF de maneira isolada tem atividade limitada, devido à reativação desta via através da sinalização do EGFR (receptor do fator de crescimento epidérmico), faz todo o sentido associarmos terapias alvo do mesmo modo que foi feito para melanoma, agora nesse novo cenário. Neste ensaio clínico randomizado, mais de 600 pacientes foram incluídos nos três braços do estudo numa proporção de 1: 1: 1 para receber encorafenibe, binimetinibe e cetuximabe (grupo de terapia tripla); encorafenibe e cetuximabe (grupo de terapia dupla); ou a escolha dos investigadores de cetuximabe e irinotecano ou cetuximabe e FOLFIRI (grupo controle). Apesar do estudo ter sido considerado positivo para o endpoint primário, este paper tem sido muito questionado diante de inúmeros problemas metodológicos, o que fez com que a NEJM recebesse, inclusive, cartas questionando como foi possível sua publicação nessa revista tão conceituada!Sejam muito bem vindos a mais um episódio do Clinical Papers Podcast. Com Tiago Biachi, Ranyell Spencer e Allan Pereira. Para ter acesso ao paper na íntegra, acesse: https://www.nejm.org/doi/full/10.1056/NEJMoa1908075

Genomic Assays in the “Real” Oncology World — Part 1: Genomic Assays and Colorectal Cancer — Featuring a roundtable discussion with Drs Emmanuel S Antonarakis, Johanna Bendell, Ian E Krop and Andrew McKenzie. Multiplex Genomic Assays and Their Role in Therapeutic Decision-Making Case: A man in his mid-80s with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed through multiple therapies is found to have CD274 (PD-L1) amplification, microsatellite instability (MSI)-high status and mutations in ATM and EGFR Effect of CD274 amplification on response to immune checkpoint inhibitors; activity of PARP inhibitors in patients with ATM mutations Advantages and limitations of multiplex genomic testing Role of serial testing to identify variations in genomic mutations or aberrations over time; potential benefit of liquid next-generation sequencing (NGS) panels Use of multiplex genomic assays by community oncologists and implications for clinical practice Optimal timing of genetic testing for patients diagnosed with metastatic disease Presentation (Dr McKenzie): Overview of multiplex genomic assay methodology Rationale for the use of serial testing and liquid assays to identify variations in genomic mutations or aberrations over time Differentiating between germline and somatic mutations in cancer tissue Perspective on the use of tissue versus liquid biopsy for genetic testing Sensitivity of liquid biopsies in detecting tumor mutations Available data exploring the impact of NGS use on patient outcomes Selection of a multiplex genomic assay for detecting genetic alterations Implications of multiplex genomic assay results for therapeutic decision-making Comprehensive Genetic Profiling and Precision Medicine for Metastatic Colorectal Cancer (mCRC) Specific biomarkers and genetic alterations routinely evaluated in clinical practice Effects of up-front multiplex genomic assay testing on outcomes for patients with mCRC Response to immune checkpoint inhibitors in patients with MSI-high mCRC (1:09:3s Presentation (Dr Bendell): Biomarker assessment in mCRC; role of multiplex testing Actionable genetic alterations in mCRC; detection of BRAF and HER2 mutations and implications for practice Rationale and indications for the assessment of MSI and DNA mismatch repair (MMR) status; emerging role of tumor mutational burden Role of liquid versus tumor biopsies for detecting genetic alterations MSI/MMR and tumor mutational burden as predictors of benefit from immune checkpoint inhibitors Emerging role for the assessment of neoantigen load Case (Dr Bendell): A man in his mid-50s with mCRC, Lynch syndrome and MSI-high status achieves a partial response to pembrolizumab as second-line therapy Case (Dr Bendell): A woman in her early 60s with microsatellite stable mCRC and a BRAF V600E mutation receives the combination of cetuximab, encorafenib and binimetinib after disease progression on FOLFOXIRI/bevacizumab Case (Dr Bendell): A man in his early 40s with HER2-positive mCRC receives trastuzumab and pertuzumab on a clinical trial after disease progression on FOLFIRI/bevacizumab and attains a partial response Novel HER2-targeted therapies under evaluation for patients with mCRC and HER2 alterations Analysis of the gut microbiome and strategies to enhance the immune response to cancer   CME information and select publications

This podcast will discuss the findings from a phase II trial of gemcitabine, cisplatin and PARP inhibitor therapy in germline BRCA/PALB2 mutant pancreatic cancer and discuss an optimal treatment strategy in this setting.   TRANSCRIPT This JCO Podcast provides observations and commentary on the JCO article “A Randomized, Multi-Center, Phase II Trial of Gemcitabine, Cisplatin with or without Veliparib in Patients with Pancreas Adenocarcinoma and a Germline BRCA/ PALB2 Mutation” by O'Reilly et al. My name is Daniel Renouf, and I am a medical oncologist at the BC Cancer Vancouver Centre in Vancouver, Canada. My oncologic specialty is pancreatic cancer. In this podcast, we will be discussing an important and evolving area that is changing our standard treatment strategies for pancreatic cancer. Progress has been slow for pancreatic adenocarcinoma, which is now the third leading cause of cancer-related death in North America and is projected to become the second leading cause of cancer-related death within the next decade. Modest gains in our treatments have been achieved with new chemotherapy combinations, including FOLFIRINOX and gemcitabine and nano-albumen bound-paclitaxel, yet still the majority of patients diagnosed with advanced disease will live for less than one year. There is a critical need for improved treatment options as well as clinically relevant predictive markers to guide our therapeutic decision making. The first clinically important predictive marker in pancreatic cancer is germline BRCA/PALB2 mutation status, which is present in 5-9% of pancreatic adenocarcinomas. Multiple translational studies and case series have demonstrated distinct molecular features of these tumors, as well as unique clinical characteristics. Germline BRCA/PALB2 mutant pancreatic adenocarcinomas have been noted to be sensitive to platinum agents and be associated with a better prognosis. Despite this data, and a general acceptance within the community that platinum agents are the preferred therapies in this setting, there is minimal prospective trial data specifically assessing the activity of platinum combinations in germline BRCA/PALB2 mutant pancreatic adenocarcinoma. At a plenary session at ASCO 2019 and its subsequent publication, the POLO trial assessed the role of maintenance therapy with a poly-ADP ribose polymerase (PARP) inhibitor (olaparib), compared to placebo, in patients with metastatic pancreatic adenocarcinoma and germline mutations in BRCA/PALB2 who had responded or had stable disease after initial therapy with FOLFIRINOX. This was a positive trial, demonstrating that maintenance olaparib significantly improved progression-free survival compared to placebo. There was no difference noted in overall survival, but this data was not yet mature. The role of combining a PARP inhibitor with platinum-based chemotherapy as upfront treatment in this patient population is yet to be defined.  A previous Phase I trial of gemcitabine, cisplatin and the PARP inhibitor veliparib determined a recommended phase II dose for velipirib in this combination and demonstrated promising efficacy in germline BRCA-mutant pancreatic adenocarcinoma. In the article that accompanies this podcast, Dr. O’Reilly and colleagues report on the results of a phase II prospective trial comparing gemcitabine and cisplatin versus gemcitabine, cisplatin and veliparib in patients with advanced pancreatic adenocarcinoma with germline aberrations in BRCA/PALB2. In the trial, patients with locally advanced or metastatic pancreatic cancer who had not received chemotherapy in the advanced setting, had a good performance status, and who harbored germline aberrations in BRCA/PALB2 were randomized. A total of 50 patients were enrolled, and the results demonstrated good efficacy in both arms, with a response rate of 74.1% in the veliparib arm and 65.2% in the control arm. Median progression-free survival was 10.1 months and 9.7 in the veliparib and non-veliparib arms respectively, and median overall survival was 15.5 and 16.4 months. Of note, for the entire cohort, 2-year overall survival was notably high at 30.6%, and 3-year overall survival was 17.8%. Grade 3-4 toxicities, including neutropenia, thrombocytopenia, and anemia were greater in the veliparib arm. The authors concluded that gemcitabine and cisplatin demonstrated significant activity in BRCA/PALB2 germline mutant pancreatic adenocarcinoma, and the addition of concurrent veliparib did not improve efficacy. Given this promising data, it was concluded that gemcitabine and cisplatin should be considered a standard treatment for BRCA/PALB2 germline mutant pancreatic adenocarcinoma. This is an important trial, as it is one of the first to specifically assess platinum chemotherapy prospectively in this patient population and has important implications for treatment strategies for pancreatic cancer, the first of which is that testing for germline BRCA/PALB2 mutations should now be considered standard of care for all newly diagnosed pancreatic adenocarcinomas. Not only does this have important treatment implications for the patient; it also has strong relevance to the patients’ family members, as it was found to also harbor a germline BRCA/PALB2 mutation. Screening and potential prevention strategies could be considered for other cancers, such as breast and ovarian. Secondly, if a patient is found to have a germline BRCA/PALB2 mutation, the data from this trial in combination with the body of literature in this setting would suggest that first line therapy with a platinum agent should be considered. In this setting, one could consider either FOLFIRINOX or gemcitabine and cisplatin. The efficacy of gemcitabine and nano albumen bound-paclitaxel in this patient population is not clearly defined, but in the context of data from other disease sites also demonstrating increased sensitivity to platinum in this patient population, and given many patients with advanced pancreatic adenocarcinoma are often not well enough to received multiple lines of therapy, a first line platinum combination should be strongly considered. Thirdly, this trial demonstrates that there is no additional benefit from adding a PARP inhibitor to chemotherapy in this setting, but there is added toxicity, and thus this strategy should not be considered at this time. Finally, given that toxicity from platinum-based chemotherapy is cumulative, the question of an optimal maintenance strategy remains. The POLO trial demonstrated that there is activity and a progression-free survival benefit when using olaparib as a maintenance post upfront platinum-based chemotherapy when compared to placebo, and therefore this represents one potential strategy. One criticism of the POLO trial is that many centers do not stop treatment and instead continue therapy without the platinum after an initial response. In patients responding to initial treatment with FOLFIRINOX, maintenance FOLFIRI is often considered. Data from a second line trial of FOLFIRI with or without veliparib presented as a poster discussion at ASCO 2019 by Dr. Chiorean and colleagues noted that BRCA/PALB2 mutant tumors also appear to have increased sensitivity to FOLFIRI. At this time, the optimal maintenance strategy after upfront platinum therapy is yet to be fully defined, and further research in this setting is needed. In addition, to what extent these strategies should be applied to patients with pancreatic adenocarcinomas that are germline BRCA/PALB2 wildtype but have other homologous recombination deficiency defects requires further investigation. In summary, this is an exciting time in pancreatic adenocarcinoma as we now have a clinically important biomarker to guide treatment strategies. This important trial by Dr. O’Reilly and colleagues further solidifies the importance of BRCA/PALB2 germline testing in pancreatic adenocarcinoma and that first line platinum-based chemotherapy should be considered in these patients. This concludes this JCO Podcast. Thank you for listening.

A combinação de anticorpos monoclonais com quimioterapia oferece benefícios para pacientes com tumores avançados ou metastáticos. HOWEVER qual deles tem maior eficiência em pacientes não tratados previamente? Estamos falando do cetuximab e bevacizumab novamente! Estamos quase lá! O objetivo é fazer um “background” sobre o assunto e discutirmos em breve a questão da lateralidade para câncer colorretal (ccr). O SWOG Trial, publicado no JAMA em 2017, teve o objetivo comparar a combinação de cetuximab vs. bevacizuma com FOLFIRI ou FOLFOX no tratamento de pacientes com ccr “KRAS wyld-type”. Siga-nos nas redes sociais e faça seus comentários! Sejam muito bem vindo a mais um episódio do Clinical Papers Podcast! Para saber mais sobre esse paper, acesse o link abaixo e tenha acesso grátis na íntegra! https://www.ncbi.nlm.nih.gov/pubmed/28632865

Dr. Osama Rahma, an Assistant Professor of Medicine at Harvard Medical School, Dana-Farber Cancer Institute, discusses the role of MSI in gastric cancer. TRANSCRIPT This JCO Podcast provides observations and commentary on the JCO article “Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability as a Biomarker in Gastric Cancer” by Pietrantonio et al. My name is Osama Rahma, and I am an Assistant Professor of Medicine at Harvard Medical School, Dana-Farber Cancer Institute in Boston, Massachusetts. My oncologic specialty is Gastrointestinal Cancer and Cancer Immunotherapy. Despite the advances in surgical approach and perioperative multimodalities in gastric cancer, the recurrence rate remains over 50%. While many patients benefit from perioperative chemotherapy many others don’t derive such benefits and experience toxic side effects. Accordingly, there is an unmet need to identify prognostic markers to guide  chemotherapy decisions in the neoadjuvant and adjuvant settings. Microsatellite instability has been well established as a prognostic marker in colon cancer that correlates with better overall survival and potential lack of benefit from adjuvant chemotherapy in stage II disease. The question is whether microsatellite instable gastric tumors have similar behavior? To answer this question, subgroups analyses of patients with MSI high tumors were performed in both the MAGIC and the CLASSIC trials which established perioperative ECF chemotherapy in non-Asian population and adjuvant capecitabine and oxaliplatin in Asia, respectively as the standard of care in resectable gastric cancer. Although MSI tumors were found to be less likely to benefit from chemotherapy, the low incidence of MSI tumors in both trials of 8-10% made it very challenging to draw  meaningful conclusions.   In the article that accompanies this podcast, Pietrantonio et al performed individual patient level data meta-analysis testing the prognostic significance of microsatellite instability in both the MAGIC and CLASSIC trials. In addition, the analysis included the ARTIST study, which tested adding radiation to adjuvant capecitabine and cisplatin in Asia and the ITACA-S study which tested adjuvant FOLFIRI, docetaxel and cisplatin vs 5-fluorouracil and folinic acid in Europe in radically resected gastric cancer. The meta-analysis included 1556 patients, 63% Asian and 37% Europeans. Patients were stratified using microsatellite instability status and based on whether they received multimodality therapy in all 4 trials or surgery only in the MAGIC and CLASSIC trials. 7.8% of patients had MSI high tumors and  70.8 % received multimodality treatment. Consistent with prior reports of individual trials, patients with MSI high tumors had better outcomes compared to MSI low or MSS tumors. Specifically, the 5-year disease free survival rate was 71.8% vs 52.3% and 5-year overall survival was 77.5% vs 59.3%. MSI remained a significant independent prognostic factor for improved disease-free survival and overall survival in a multivariate analysis in addition to Asian ethnicity, low TNM staging, and receiving multimodality therapy. In addition, MSI was noted to be more prevalent in the Asian population and was a better prognostic factor in Asians compared to Europeans.   Importantly, MSI high tumors did not benefit from perioperative chemotherapy with 5-year disease free and overall survival of 70% and 75%, respectively for those who received chemotherapy compared to 77% and 83% for MSI high patients who did not receive chemotherapy. In contrast patients with MSI low or MSS experienced benefit from perioperative chemotherapy compared to surgery alone. Finally, MSI status did not affect post-recurrence survival. However, this was limited by the small number of MSI high patients who experience disease recurrence.   This study has several limitations including its retrospective nature, the relatively small number of patients with MSI high tumors of 121, and the heterogenicity of administered treatment in the 4 trials including different regimens of neoadjuvant and adjuvant chemotherapy with or without radiation. In addition, D1 surgery was performed in Europe while D2 surgery was performed in Asia. In summary, I think this study supports the adoption of microsatellite testing as a routine biomarker in patients with operable gastric cancer. The result of microsatellite testing should be discussed in a multidisciplinary fashion since perioperative chemotherapy may result in more harm than benefit in MSI high tumors. This study among others highlights the unique behavior of microsatellite instable tumors which is driven by their unique immune profile including increased T-cell infiltration and activation due to higher mutational load and neoantigens compared to microsatellite stable tumors. PD-1 inhibitors are effective in more than 50% of MSI tumors in the advanced setting and in 15-25% of gastric tumors with positive PD-L1 expression.  Accordingly, future clinical trials should stratify gastric cancer patients based on their microsatellite status and PD-L1 expression while incorporating immunotherapy in the early disease setting.   This concludes this JCO Podcast. Thank you for listening.

Dra. Chiara Cremolini comenta os resultados do estudo que comparou encorafenibe + cetuximabe com ou sem binimetinibe versus tratamento padrão com irinotecano ou FOLFIRI mais cetuximabe no tratamento de câncer colorretal metastático com mutação de BRAF, os resultados iniciais do estudo MOUNTAINEER com trastuzumabe e tucatinibe no tratamento do câncer colorretal metastático com amplificação de HER-2, e o valor prognóstico e preditivo para a duração do tratamento adjuvante de câncer colorretal a partir da análise do DNA tumoral circulante que foram apresentados no estudo de fase III IDEA-FRANCE.

Cetuximabe e Bevacizumabe têm demonstrado aplicabilidade clínica no câncer colorretal. A maioria dos estudos no entanto utiliza a associação dessas drogas com esquemas contendo oxaliplatina. O FIRE-3 foi um estudo publicado na THE LANCET Oncology em 2014 que comparou o uso de ambas as terapias com FOLFIRI avaliando como endpoint primário taxa de resposta ao RECIST para pacientes EC IV KRAS wild-type. Não se preocupe com esses nomes esquisitos! Eu e Tiago explicaremos pra você! Esse é o primeiro de dois estudos que falaremos com o objetivo de tratar do tema “lateralidade em câncer colorretal”. Veja também como você deve se comportar diante de um estudo patrocinado. O que isso pode implicar em análise e divulgação de dados. Para saber mais sobre esse paper, acesse o link abaixo e tenha acesso grátis na íntegra! https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70330-4/fulltext Siga-nos nas redes sociais e faça seus comentários! Sejam muito bem vindo a mais um episódio do Clinical Papers Podcast!

Video proceedings from the first in a series of 6 integrated symposia held at the 2019 ONS Annual Congress. Featuring perspectives from Ms Jessica Mitchell, Dr Eileen M O'Reilly, Dr Philip A Philip and Ms Amanda Wagner. Introduction 0m0s Program overview: Dr Love Colorectal Cancer (CRC) (5:43) Case (Ms Wagner): A man in his mid-70s with metastatic appendiceal carcinoma who received third-line TAS-102 after disease progression on FOLFIRI/bevacizumab and FOLFOX/bevacizumab (8:11) Case (Ms Mitchell): A man in his early 40s with MSI-high metastatic CRC who experienced a dramatic response to pembrolizumab (29:59) Hepatocellular Carcinoma (HCC) (36:14) Case (Ms Wagner): A man in his mid-40s with metastatic HCC who developed hand-foot syndrome while receiving sorafenib (38:21) Case (Ms Mitchell): A woman in her mid-60s with metastatic HCC who had a good response to nivolumab but developed arthralgias (58:07) Pancreatic Cancer (1:04:33) Case (Ms Mitchell): A woman in her mid-70s with locally advanced pancreatic cancer who received neoadjuvant FOLFIRINOX (1:04:47) Case (Ms Wagner): A man in his mid-60s with metastatic pancreatic cancer who received nab paclitaxel/gemcitabine and nal-IRI (1:12:13) Gastroesophageal Cancers (1:20:20) Case (Ms Wagner): A man in his early 70s with metastatic esophageal adenocarcinoma who received FOLFOX followed by paclitaxel/ramucirumab upon disease progression (1:20:43) Case (Ms Mitchell): A woman in her early 60s with metastatic gastric cancer who experienced an excellent response to pembrolizumab but developed autoimmune hypothyroidism (1:24:02) Select publications

A roundtable discussion featuring perspectives from Drs Tanios Bekaii-Saab and Alan P Venook on emerging research and cases from their practices. Introduction — Indications for and Practical Implementation of Biomarker Analysis for Patients with Metastatic Colorectal Cancer (mCRC) Biomarker assessment for patients with mCRC (0:00) Perspectives on genomic testing platforms used to perform biomarker analysis for mCRC (3:16) Role of rebiopsy and repeat biomarker assessment for patients with progressive mCRC (7:11) Biology of mCRC and Role of Tumor Sidedness in First- and Later-Line Decision-Making Implications of RAS testing for selection of therapy (10:22) Tumor sidedness and therapeutic decision-making (13:55) Similarities and differences in the design and primary endpoints of the Phase III CALGB-80405 and FIRE-3 trials evaluating first-line chemotherapy in combination with cetuximab and/or bevacizumab for KRAS wild-type mCRC (18:12) Prognostic and predictive relevance of primary tumor sidedness in patients with RAS wild-type mCRC on the CALGB-80405 and FIRE-3 trials (22:11) Efficacy of EGFR inhibitor- versus bevacizumab-based treatments for left- versus right-sided RAS wild-type mCRC (23:28) Choosing between EGFR inhibitor- and bevacizumab-based treatments as first- and second-line therapy for patients with symptomatic left-sided RAS wild-type mCRC (31:39) Case (Dr Venook): A woman in her thirties with left-sided RAS wild-type mCRC receives first-line FOLFOXIRI (40:14) Therapeutic options for younger patients with left-sided RAS wild-type mCRC and disease progression on first-line FOLFOXIRI (43:58) Case (Dr Bekaii-Saab): A man in his sixties with left-sided RAS wild-type mCRC and disease progression after 2 years of first-line “stop-and-go” FOLFIRI/bevacizumab receives FOLFIRI/panitumumab (45:56) Activity of cetuximab versus panitumumab and practical considerations for use (49:37) Clinical experience with and management of EGFR inhibitor-associated dermatologic toxicities (51:45) Second opinion: Second-line therapy options for patients with left-sided RAS wild-type mCRC and disease progression on first-line FOLFIRI/bevacizumab (55:48) Faculty perspectives on therapeutic algorithms for first- through later-line therapy for left- versus right-sided RAS wild-type mCRC (1:00:43) Current and Future Treatment Options for Patients with BRAF Mutations Efficacy of EGFR inhibition in patients with mCRC and atypical (non-V600E) BRAF mutations (1:08:18) Clinical presentation of and prognosis for patients with mCRC and a BRAF V600E tumor mutation (1:12:22) Activity and tolerability of EGFR/MEK/BRAF-inhibitor combinations in patients with mCRC and a BRAF V600E tumor mutation (1:13:59) Importance of BRAF testing in mCRC; strategies for first-line therapy and beyond (1:16:13) Improved tolerability with triplet EGFR/MEK/BRAF-inhibitor combinations in comparison to anti-EGFR monotherapy or doublet combinations (1:19:54) Case (Dr Venook): A woman in her forties with mCRC, a BRAF V600E tumor mutation and rapid disease progression on first-line FOLFOXIRI/bevacizumab attains long-term disease stabilization with encorafenib/binimetinib/panitumumab (1:22:13) Case (Dr Bekaii-Saab): A man in his fifties with mCRC and a BRAF V600E tumor mutation receives second-line encorafenib/binimetinib/cetuximab on a clinical trial (1:23:27) Optimal Management of Microsatellite Instability (MSI)-High or DNA Mismatch Repair-Deficient mCRC Assessment of MSI status and tumor mutation burden as predictors of response to immune checkpoint blockade (1:26:47) Sequencing of anti-PD-1/PD-L1 checkpoint inhibitors for MSI-high mCRC (1:33:19) Neoadjuvant ipilimumab with nivolumab for early-stage colon cancer (1:36:39) Activity and tolerability of immune checkpoint inhibitors alone and in combination in patients with MSI-high mCRC (1:37:34) Case (Dr Bekaii-Saab): A woman in her fifties with MSI-high, right-sided mCRC and a RAS mutation receives second-line pembrolizumab (1:42:11) Case (Dr Venook): A woman in her forties with Stage III CRC initially treated with adjuvant FOLFOX experiences disease progression and receives an assessment of MSI-high disease (1:46:37) Perspective on pseudoprogression in patients undergoing immune checkpoint inhibitor therapy (1:48:50) HER2 Positivity and Other Potential Biomarkers Biology and epidemiology of mCRC with HER2 amplification/mutation (1:51:16) Activity of and duration of response to dual HER2-targeted therapy in patients with mCRC and HER2 amplification/mutation (1:54:09) Therapeutic options for patients with mCRC and HER2 amplification/mutation (1:55:45) Case (Dr Venook): A man in his fifties with left-sided, RAS wild-type mCRC and HER2 amplification/mutation receives fourth-line trastuzumab/pertuzumab (2:00:13) Case (Dr Bekaii-Saab): A woman in her sixties with left-sided, RAS wild-type mCRC and HER2 amplification/mutation receives third-line trastuzumab/tucatinib on a clinical trial (2:01:57) Activity of tucatinib in patients with mCRC and HER2 amplification/mutation (2:04:40) Optimizing the risk-benefit ratios of systemic therapy options for patients with mCRC (2:07:36) Modulation of the gut microbiome to enhance response to anti-PD-1 immunotherapy; effects of antibiotics on response to immune checkpoint inhibitors (2:11:12) Select publications

Pancreatic Cancer Update – Part 2: Our interview with Dr Chiorean highlights the following topics as well as cases from her practice: Biomarker-driven and molecular-targeted therapies for patients with adenocarcinoma of the pancreas: 0m0s Rationale for the investigation of PEGPH20 in combination with pembrolizumab for previously treated hyaluronic acid (HA)-high metastatic pancreatic cancer: 4m40s Tolerability and quality of life with PEGPH20 in combination with chemotherapy; mitigation of associated thromboembolic events: 6m59s Ongoing Phase II trial of PEGPH20 with pembrolizumab for previously treated HA-high metastatic pancreatic ductal adenocarcinoma: 10m14s Testing for emerging biomarkers (eg, microsatellite instability) of response to immune checkpoint inhibitors in metastatic pancreatic cancer: 11m49s Incidence of germline BRCA mutations and response to PARP inhibition: 15m27s Case: A 55-year-old woman presents with back pain and dyspepsia and is diagnosed with borderline resectable adenocarcinoma of the pancreas: 17m55s Risk of relapse with and without adjuvant chemotherapy for patients with lymph node involvement: 24m45s Clinical experience with adjuvant FOLFIRINOX and gemcitabine/nab paclitaxel: 29m46s Activity, tolerability and dosing of adjuvant FOLFIRINOX: 31m39s Role of neoadjuvant chemotherapy in the treatment of resectable or borderline resectable adenocarcinoma of the pancreas: 33m55s Case: A 69-year-old woman with metastatic pancreatic cancer receives nal-IRI/5-FU/LV after experiencing disease progression on gemcitabine/nab paclitaxel: 38m26s Response and tolerability with FOLFIRINOX compared to gemcitabine/nab paclitaxel: 41m49s Second-line therapy options for metastatic pancreatic cancer: 46m59s SWOG-S1513: An ongoing Phase II trial evaluating FOLFIRI alone versus modified FOLFIRI with the PARP inhibitor veliparib as second-line therapy for metastatic pancreatic cancer: 50m42s Investigation of CDK4/6 inhibition-based therapies for advanced pancreatic cancer: 52m21s Second opinion: A 53-year-old man of Ashkenazi Jewish descent with a strong family history of BRCA mutation-associated cancers presents with metastatic pancreatic cancer and is found to harbor a germline BRCA2 mutation: 54m34s Importance of palliative care in managing the symptoms of pancreatic cancer: 1h1m22s Select publications

David Henry, MD, welcomes Daniel G. Haller, MD, to rehash research from ESMO 2018 as well as the way the meeting itself was run.  And Ilana Yurkiewicz, MD, stops by for this week’s Clinical Correlation. Dr. Yurkiewicz is a Hematology Fellow at Stanford and is also a columnist at MDedge Hematology/Oncology. More from Dr. Yurkiewicz here. Contact us: podcasts@mdedge.com MDedge on Twitter: @mdedgehemonc Dr. Ilana Yurkiewicz on Twitter: @ilanayurkiewicz SHOW NOTES By Emily Bryer, DO Resident in the department of internal medicine, University of Pennsylvania Health System CheckMate 142: Durable clinical benefit with nivolumab plus low-dose ipilimumab as first-line therapy in microsatellite high (MSI-H) and non-MSI-H colon cancer Phase 2 study included 45 patients with metastatic colorectal cancer Overall response rate (primary end point) was 60% and disease control rate was 84% Almost every patient had some response and the therapy was well-tolerated https://bit.ly/2TljlQE    Tribe 2: FOLFOXIRI plus bevacizumab followed by reintroduction of FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab Phase 3 study of 654 patients with unresectable metastatic colorectal cancer Progression free survival (primary end point) of FOLFOXIRI regimen was 18.9 months, compared with 16.2 months of the FOLFOX then FOLFIRI regimen Side effects of FOLFOXIRI: febrile neutropenia, neutropenia, GI toxicities https://bit.ly/2EMKBOa    Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomized, double-blind, placebo-controlled, phase 3 trial Phase 3 study included 506 patients with metastatic gastric cancer Trifluridine/tipiracil (oral drug) provided a 2-month overall survival advantage (primary end point), compared with placebo Major side effect: neutropenia https://bit.ly/2tW7PMI    Safety and clinical activity of 1L atezolizumab plus bevacizumab in a phase 1b study in hepatocellular carcinoma (HCC) Phase 1B study included 100 patients with HCC who had not received prior therapy Disease control rate was high as was duration of response Primary outcomes included safety and efficacy The overall response rate was 34% and the most common side effect was hypertension https://bit.ly/2EEPKaO   

In this episode, I summarize how I discovered my cancer returned in my liver.  I recount the process, the emotions, and side effects from the end of 2018.Contact info to send questions to the podcast are listed below.Email: vixmixpodcast@gmail.comVoiceMail: 505-333-8232Instagram: @vixmixpodcast

Prof Van Cutsem meets with ecancertv at ESMO 2016 to discuss the different treatment profiles of left or right sided colon cancers, as determined through the CRYSTAL study. He describes how, depending on the tumour locations in reference to the splenic fracture, left sided tumours responded more to the cetuximab FOLFIRI being administered in the trial, and considers how sidedness as a substitute for biomarkers is only a starting point for prognosis. Dr Van Cutsem reflects on other presentations from the conference, how they will guide clinical development and may result in improvements of care.

Dr Iveson speaks with ecancer at ASCO 2017 about results from the SCOT trial, a non-inferiority assessment of adjuvant oxaliplatin chemotherapy for 3 or 6 months to treat colorectal cancer. He describes how, by meeting these non-inferiority endpoints, 3 months of oxaliplatin can reduce cost for healthcare providers and improve patient quality of life, with less risk of peripheral neuropathy. The SCOT trial contributes to a larger international trial schema called IDEA, an international collaborative assessment of oxaliplatin with capecitabine or FOLFIRI at different fractions and staging. Findings within IDEA have identified high and low risk groups, Dr Iveson encourages to be considered eligible for 3 months CapOx.

Franco Mussida, ex PFM, presenta il suo progetto "CO2-controllare l'odio" che porta nelle carceri l'emozione della musica; Fabio Concato e Fabrizio Bosso raccontano il loro incontro sul palco che ha portato alla realizzazione dell'album "Non smetto di ascoltarti"; Gli Afterhours e il loro nuovo lavoro "Folfiri o Folfox" spiegato da Manuel Agnelli e Rodrigo D'Erasmo

Prof Peeters talks to ecancertv at ASCO 2014 about the updated analysis of KRAS/NRAS and BRAF mutations in study 20050181 of panitumumab plus FOLFIRI for second-line treatment of metastatic colorectal cancer.

Dr Volke Heinemann talks to ecancer managing editor, Prof Gordon McVie, at ASCO 2013 about the German phase III clinical trial FIRE-3. The study found that first-line cetuximab plus FOLFIRI chemotherapy (folinic acid, fluorouracil, irinotecan) offers a roughly four-month survival advantage for patients with metastatic colorectal cancer, compared with bevacizumab plus FOLFIRI. The targeted drugs cetuximab and bevacizumab, both in combination with chemotherapy, are approved and commonly used as initial therapy. Until this study, it had been unclear which approach is better for patients with non-mutated forms of the KRAS gene.

MeetTheProfessors.com – 65yo w/Dukes C; rcvd postop adj. 5-FU/leu; 5y later, began FOLFOX6 w/bev for liver mets; partial response; b/c of neuropathy stopped chemo after 9 cycles, continued bev; 3mo later, liver lesions progressed and began FOLFIRI w/bev