Podcasts about FOLFIRINOX

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Play Episode Listen Later Feb 6, 2025 21:13

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

How to Approach and Treat Pancreatic Cancer

Oncology Brothers

Play Episode Listen Later Nov 21, 2024 22:27

Welcome to the Oncology Brothers podcast! In this episode, hosts Drs. Rohit and Rahul Gosain are joined by Dr. Eileen O'Reilly, a leading medical oncologist and section head of hepatobiliary and pancreatic cancer at Memorial Sloan Kettering Cancer Center. Together, they delve into the complex treatment landscape of pancreatic cancer. Episode Highlights: ⁠ ⁠The initial workup for newly diagnosed pancreatic cancer patients, including the importance of imaging and genetic testing. ⁠ ⁠Treatment paradigms for early-stage, borderline resectable, and metastatic pancreatic cancer. ⁠ ⁠The role of multi-agent chemotherapy, including modified FOLFIRINOX and gemcitabine-nab-paclitaxel. ⁠ ⁠Insights into managing patients with high bilirubin levels and the considerations for dose adjustments. ⁠ ⁠The emerging role of targeted therapies and the significance of comprehensive genetic testing in treatment decisions. Join us as we explore the latest standards of care, the importance of a multidisciplinary approach, and the potential of new therapies in improving outcomes for patients with pancreatic cancer. Don't forget to like, subscribe, and check out our other episodes for more insights on oncology topics, conference highlights, and recent treatment approvals! Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

Lisata Therapeutics CEO encouraged by progress on pancreatic cancer trial

Proactive - Interviews for investors

Play Episode Listen Later Jun 14, 2024 4:12

Lisata Therapeutics Inc. CEO David Mazzo talked with Proactive's Stephen Gunnion about the latest milestone in the company's Phase 1b/2a CENDIFOX trial. Mazzo shared that Lisata has completed patient enrollment for the pancreatic cancer cohorts in the phase 1B/2A clinical trial. This investigator-initiated trial, led by Dr Anup Kasi at The University of Kansas Cancer Center, is evaluating the safety and efficacy of certepetide (formerly LSTA1) in combination with FOLFIRINOX-based therapies for pancreatic, colon, and appendiceal cancers. Mazzo highlighted that the trial will enbable the collection of pre- and post-treatment biopsies of tumors. He also mentioned ongoing efforts to complete enrollment in two additional cohorts focusing on colorectal cancer and other tumor types, expecting these to be completed by the end of the year. Expressing his optimism, Mazzo noted the encouraging progress and enthusiasm surrounding the trial, which is drawing patients from the Kansas City area despite competition from other studies. He anticipates that preliminary results will be available by the end of the year, pending the timely processing of biopsies by external laboratories. Visit Proactive's YouTube channel for more videos, and don't forget to give the video a like, subscribe to the channel, and enable notifications for future content. #LisataTherapeutics #DavidMazzo #CancerResearch #ClinicalTrials #PancreaticCancer #Surufatinib #CancerTreatment #Biotech #MedicalResearch #ProactiveInvestors #ProactiveInvestors #invest #investing #investment #investor #stockmarket #stocks #stock #stockmarketnews

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Updates In RCC, Pancreatic Cancer, And Skin Cancer In SOT

OncoPharm

Play Episode Listen Later Mar 28, 2024 13:44

Discussing four papers that caught our eyes from the last few weeks: Pazopanib vs. placebo following metastatectomy. Always concerning when placebo has an OS advantage. ECOG-ACRIN E2810: https://doi.org/10.1200/JCO.23.01544 Gemcitabine vs. Gem + Paclitaxel (Taxol) in pancreatic cancer patients after FOLFIRINOX: https://doi.org/10.1200/JCO.23.00795 An RNA assay to predict gemcitabine sensitivity: https://doi.org/10.1200/JCO.22.02668 Management of skin cancers with ICIs in kidney transplant patients: https://doi.org/10.1200/JCO.23.02570

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108: Rob Caruano - Pancreatic Cancer Survivor - New York, New York, USA

covid-19 united states new york city cancer mri cancer survivors cancer treatment chemotherapy pancreatic cancer yorknew pancreatitis folfirinox

Play Episode Listen Later Jan 27, 2024 24:27

Rob Capuano woke up one night with a severe pain in his stomach. He wanted to be seen at an urgent care, but due to COVID, the facility couldn't admit him. When he was seen, he had to insist on an MRI, which resulted in his diagnosis of pancreatic cancer. Between surgery and chemotherapy, Rob achieved survivorship. He is also thankful that the hospital where he was treated was sensitive to issues tied to his being a married gay man, because, says Rob, not all health care facilities have staffers with those sensitivities. Rob says his health is very close to its pre-diagnosis level, and works as an advocate for cancer patients.

Tumor Mutational Burden and Advanced Pancreatic Cancer

JCO Precision Oncology Conversations

Play Episode Listen Later Jan 24, 2024 27:18

JCO PO author Dr. Amit Mahipal shares insights into his JCO PO article, “Tumor Mutational Burden in Real-world Patients with Pancreatic Cancer: Genomic Alterations and Predictive Value for Immune Checkpoint Inhibitor Effectiveness.” Host Dr. Rafeh Naqash and Dr Mahipal discuss real world evidence of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma. TRANSCRIPT Dr. Rafeh Naqash: Welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, Social Media Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center, University of Oklahoma. Today we are joined by Dr. Amit Mahipal, Professor of Medicine and Director of GI Oncology at the Case Western Reserve University in Seidman Cancer Center. Dr. Mahipal is also the author of the JCO Precision Oncology article titled "Tumor Mutational Burden in Real World Patients with Pancreatic Cancer: Genomic Alterations and Predictive Value of Immune Checkpoint Inhibitor Effectiveness." Our guest disclosures will be linked in the transcript. For the sake of this conversation, we will refer to each other using our first names. So Amit, welcome to our podcast and thank you for joining us today. Dr. Amit Mahipal: Thanks for having me here. Dr. Rafeh Naqash: Excellent. We came across your article in JCO Precision Oncology and it really aroused my interest because the topic and the audience that it caters to is very important in the current times. Because immunotherapy generally is considered- pancreas cancer the graveyard in immunotherapy in essence, based on what I have seen or what I have encountered. And now you're the expert here who sees people with pancreas cancer or has done a lot of work in pancreas cancer research side. So can you tell us the context of this work and why you wanted to look at immune checkpoint inhibitors in pancreas cancer? Dr. Amit Mahipal: Absolutely, Rafeh. As you mentioned, pancreatic cancer is considered a what we call "cold tumors." They don't typically respond to immunotherapy. And when we talk to our patients or patient advocates, as you know, patients are very excited about immunotherapy. Immunotherapy has transformed the treatment for a lot of different cancers and not only has increased survival, but the quality of life is so much different than with chemotherapy. This work came from based on the KEYNOTE-158 trial, which was a tumor-agnostic trial which accrued patients who had TMB high tumor. What that means is that tumor mutation had more than 10 mutations per megabase. And what happens is because of that trial, more than 200 patient trial, the FDA actually approved this immunotherapy or pembrolizumab as a single agent pembrolizumab for any patient with a solid tumor who has high TMB. Again, tumor mutation burden, more than 10 mut/Mb. This question comes in now. Does this apply to our pancreatic cancer patient groups? Especially as we know these are "cold tumors" that typically do not respond. There have been multiple trials looking at immunotherapy, single agent, dual immunotherapy agents, as well as combinations with chemotherapy, with somewhat very, very limited success. So that was kind of the basis. So we wanted to look at this retrospective kind of review of a big database to see how many patients we can find who have high TMB and see in that patient population is immunotherapy really active based on the FDA approval or is pancreatic cancer not a tumor where we should try immunotherapy unit as a selective group. Dr. Rafeh Naqash: Thank you for that explanation. Taking a step back again, since you see these individuals with pancreatic cancer I imagine day in and day out in the space of drug development, what is the general current standard of care approach for individuals with pancreas cancer in your clinic? I'm talking about what are the most common approaches that you utilize that seem to be working or have FDA approvals in the pancreas cancer space. Dr. Amit Mahipal: As with any tumor, the first thing is obviously staging. So depending on whether we're dealing with early stage or advanced stage and what are the goals of treatment. At this point, the only thing that can cure pancreatic cancer patients that would be considered conventional therapy is surgical resection. So any patient who is a candidate for surgical resection is in a different bucket compared to advanced patients. For early stage patients, we try to do what we call neoadjuvant treatment or neoadjuvant chemotherapy. We shrink the tumor or at least maintain it, look at the biology of the disease, and then take them to surgery, which typically involves a Whipple procedure if it's a head of the pancreatic mass. Moving on to advanced patients, that's where we know the goal of treatment is palliative to increase survival, but unfortunately, most of the times we cannot cure them. And there the standard of care options include systemic chemotherapy. We have two typical regimens that we use, one is called FOLFIRINOX, which is a three-drug regimen of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan. And another regimen is gemcitabine plus abraxane, which is a two-drug regimen of gemcitabine plus abraxane. These are considered the standard of care. Unfortunately, the median survival even with the best standard of care chemotherapy is only about a year, 12-13 months, depending on what trials we look at. Dr. Rafeh Naqash: I still remember some of these regimens from my fellowship, where we had to decide which to give to each individual based on their performance status and clinical status, etc. But now I can see a lot of ongoing drug development in the space of pancreas cancer. I'm guessing that's why you wanted to assess both the molecular genomic landscape of pancreas cancer in this study and also look at the immune biomarker aspect. Could you tell us a little bit about the Foundation Medicine Clinical Genomic Database? How did you identify the patients, how many patients did you identify, what you narrowed down in the criteria, and the eventual sample size of what you were looking at? Dr. Amit Mahipal: FoundationOne has a rich database. They have two or three things. One is a genomic database only. So in our clinical practice, I think it's some sort of next-generation sequencing or mutational testing for all patients with advanced solid tumors. All of these goes into their database. All of the samples that are sent to FoundationOne that goes into their database where they know the diagnosis of the patient and the know the sequencing results of these patients. In addition, they also have a clinical database called Flatiron. Basically, they collaborated with them. Flatiron has about 280 or so cancer clinics throughout the country, so a lot of community settings and some academic sites as well. They did not only have a genomic database, but they actually have a clinical database. They have demographics, clinical features, baseline clinical features, comorbidities, what kind of treatment they received, what would be the stage of the cancer, how many months of treatment they received, and their overall survival, and so on. So from that perspective, the FoundationOne has access to this partnership with Flatiron, clinical genomic database where they have both clinical data as well as genomic database for a lot of these patients. In our study, we only focused on patients with advanced pancreatic cancer. We excluded a lot of patients who did not have sequencing results available, they cannot be performed due to lack of tissue. So the first we talked about the genomic database and we found about about 21,932 patients, so almost 22,000 patients and there we had the sequencing and we also had the data on TMB or tumor mutational burden. So here, we classified them into two groups: high TMB and low TMB. High TMB was seen in 1.3% of the patients, and about 98.3% of the patients had low TMB. Here we looked at the genomic alterations between the two groups. So these are like our genomic group, so to speak of about 22,000 patients. And among them, as mentioned, that the clinical data was available for about 3300 patients or 3279 patients to be exact. After excluding some of those patients, we found about 51 patients who received immunotherapy. And when we say immunotherapy, it is single agent immuno checkpoint inhibitor like pembrolizumab or nivolumab. And then we classified them into high TMB versus low TMB and then we also looked at patients with high TMB and compared them to who received immunotherapy versus other therapies. Just to recap, we had about 22,000 patients where we have the genomic database and about 3300 or so patients who we have both genomic and clinical data for this patients. One of the key findings was that high TMB was present in only 1.3% of the patients, or about 293 patients out of 21,932. Dr. Rafeh Naqash: Definitely an interesting sample size that you had utilizing this resource, which, of course, is more or less real-world. It is important to gather real-world outcomes that you did. So, going to the TMB story of this paper, where you looked at immune checkpoint inhibitor use in these individuals, was there a reason why some of the individuals with low TMB were also given immune checkpoint inhibitors? From my understanding, I did see some checkpoint inhibitor use there. What could be the explanation for that? Dr. Amit Mahipal: So this data is from 2014 to 2022. So from the span of about eight or so years. And as you know, immune checkpoint inhibitors were approved in the last decade. And there were a lot of not only trials, but even in the non-trial setting, people had tried immune checkpoint inhibitors in, frankly, different tumor types because of the success in some of the common tumor types, like melanomas, lung cancer, and so on. So I agree, as of today, we probably would not use immune checkpoint inhibitors in patients with low TMB or MSS. But at that time, I think that information was not available. So people with low TMB and MSI-stable tumors also received immune checkpoint inhibitors. But those numbers are again low. So it's not very high numbers. Dr. Rafeh Naqash: Understandable. That makes it a little more clear. Now, you looked at the TMB aspect. I'm guessing you also looked at the MSI aspect of PDAC. What is your understanding, or what was your understanding before this study, and how did it enhance your understanding of the MSI aspect of PDAC? And I'm again guessing, since TMB high individuals are on the lower side percentage, so MSI high is likely to be low as well. Did you see any interaction between those MSI highs and the TMB highs on the PDAC side? Dr. Amit Mahipal: Yeah, absolutely. So we are very excited in general about MSI-high tumors for solid tumors because of their response to immunotherapy. Although I would do a caveat because we still don't know how MSI-high pancreatic cancer responds although there have been some real-world, very, very small series as well. In this study, one of the things is, is high TMB totally driven by MSI-high? That's a question that comes up, and TMB high may not matter. It's only the MSI-high that might matter. So definitely when we look at this patient population, we found that the patients who were 35-36% of patients who were TMB high also had MSI-high patients. So we do expect MSI-high patients to have a higher TMB compared to MSS patients. But there were about 66 or two-thirds of the patients who did not have MSI-high tumors and still had high TMB, as defined by, again, ten mutations per megabase. So we did see patients with MSI-stable tumors who had high TMB. And I think that was one of our biggest questions. I think MSI-high patients, we all tend to think that we would try immunotherapy even if it's in pancreatic cancer. I think what is not clear, at least from the real-world or any of the trial data, is if we were to give MSI-stable patients who have high TMB, if we give immunotherapy, are there any responses or any disease control that we see? And that was one of the reasons for this study. Dr. Rafeh Naqash: Now, one of the things that comes to mind, and again, I think you based it on the FDA approval for TMB high, which is ten mutations per megabase, as you defined earlier. I do a lot of biomarker research, and oftentimes you come across this aspect of binary versus a linear biomarker, in this case being TMB, where about ten, less than ten. Do you think, in general, an approach where you maybe have tertiles or quartiles or a biomarker, or perhaps a better approach in trying to stratify individuals who may or may not benefit from immunotherapy? Dr. Amit Mahipal: That's a great point. I think when we use ten mutations per megabase as a biomarker, as a binary endpoint, do we apply it to all tumor types? I don't think that's a fair comparison, frankly speaking. We do know that high TMB, even in different tumor types, do tend to respond a little bit better to or do have better outcomes for patients treated with immune checkpoint inhibitors in different tumor types. But what that cutoff is not known in most of the tumor types. And also, one of the problems is how do you measure TMB and is it standard across different platforms? Like I'm just giving some names like FoundationOne, Tempus, Caris, and some obviously like MSKCC and some other university-owned panels as well. And frankly, I think if you look at different panels and if you send the same tumor tissue, you will get different measurements. So I think standardization is a problem as well. In one of the studies involving cholangiocarcinoma, for example, we found that a TMB of 5 was enough to have an additive effect of immunotherapy, same with chemotherapy, so to speak. But again, this needs to be validated. So you're absolutely correct. I don't know why we use the binary endpoint, but on the same token, the binary endpoint is easy to understand as a clinician. Like, “Hey, someone has this, do this, not this.” And when we look into a continuous range, I think the benefit obviously varies between high and low, different tertiles, and becomes somewhat challenging. How do you classify patients and what treatments to give? So I think in clinical decision-making, we like the cutoffs, but I think in reality, I don't know if the cutoff is a true representation. And maybe with the more use of AI or computing, we can just input some values, and then it can tell us what the best treatment option might be for the patient. But that's way in the future. Dr. Rafeh Naqash: That would definitely be the futuristic approach of incorporating AI, machine learning perhaps, or even digital pathology slides in these individuals to ascertain which individuals benefit. Going back to your paper, could you highlight some of the most important results that you identified as far as which individual is better, whether it was immunotherapy, and you've also looked at some of the mutation co-mutation status. Could you highlight that for our listeners? Dr. Amit Mahipal: So the first thing we looked at was the genomic database of almost 22,000 patients, and then we classified them into high TMB and low TMB, with about 300 patients in the high TMB group and the rest in the low TMB group. And what we found was, talking about again in the genomic database, that patients who have high TMB actually have low KRAS mutation. So if we think about KRAS mutation, pancreatic cancer, almost 85% or so of patients have KRAS mutation who have pancreatic adenocarcinoma. So patients in this subgroup, so in the high TMB group, only about two-thirds of the patients had KRAS mutation, compared to 92% of the patients with low TMB who had KRAS mutation. So just giving that perspective. So KRAS mutation, which is the most common mutation in pancreatic cancer and is a driver mutation, their rates vary differ from the high TMB group versus the low TMB group. And then in addition, in the high TMB group, we found higher rates of BRCA mutation, BRAF mutation, interestingly, and then obviously from the DNA damage repair genes like PALB2 mutation, MSH2 or MSH6, MLH1, and PMS2. So all these mismatch repair protein mutations were higher. As I mentioned before, one-third of the patients with high TMB also had MSI-high. So it's not a totally unexpected finding. I think the biggest finding was that we found more KRAS wild-type pancreatic adenocarcinoma in the high TMB group, almost a third. And those tend to have different targetable mutations like BRCA2, BRAF, and PALB2 mutations. So I think one of the interesting findings is that patients in the high TMB group actually tend to have KRAS wild-type or less KRAS mutations. So they're not necessarily KRAS-driven tumors, and they have a higher chance of having other targetable mutations like BRAF and so on, for which we have therapies for. So it's always something to keep in mind. Dr. Rafeh Naqash: Would you think that from a DDR perspective, the mutations that you did identify that were more prevalent in individuals with high TMB, do you think that this is linked to perhaps more DNA damage, more replication stress, more neoantigens leaning toward more tumor mutation burden perhaps? Or is there a different explanation? Dr. Amit Mahipal: For sure. As we said, MSI-high tumors have mutations in the DNA damage repair pathway and they definitely tend to have higher TMB. So I don't think that is very surprising that we found PALB2, or other MMR genes like MSH2, MSH6, MLH1, and PMS2 at much higher rates. I think the interesting finding is the fact that the KRAS wild-type and having BRAF alterations at least that's not suspected to definitely increase TMB. Although if we look at colorectal cancer, BRAF mutation and MSI are somewhat correlated to patients with BRAF mutations and to have high rates of MSI-high tumors. But that's not the case in pancreatic cancer. We also found an increase in BRCA2 mutations as well. So I agree that the DNA damage pathway repair gene alteration is not unexpected because they tend to increase TMB, but I think the other mutations were interesting. Dr. Rafeh Naqash: And I think one other aspect of this, which I'm pretty sure you would've thought about is the germline implications for some of these mutations where you could very well end up screening not only the individual patient, but also their family members and have measures in place that we're trying to enhance screening opportunities there. In your current practice, you are at an academic center but I'm talking about in general with your experience, how common is it to sequence broad sequencing panels in individuals with pancreas cancer? The reason I asked that is I do a lot with lung cancer and even now despite having all those targets in lung cancer which sort of paved the pathway for targeted therapy in many tumor types, we still don't see a full uptake for NGS Phase I drug development. And I get a lot of referrals from outside and I often see that it's a limited gene panel. So what is your experience with pancreatic cancer? Dr. Amit Mahipal: We kind of changed our practice. Similar to you, I'm involved in drug developments. I've been a big proponent of NGS for almost a decade now, when didn't even have targeted therapies but these companies first came in and they're like, “Okay. We're very very low chance.” But now obviously, we transformed the treatment for a lot of different cancers. Especially lung cancer, you don't sometimes even start treatment before you get an NGS panel like you said in situ. So what we're finding, at least for pancreatic cancer, as you know, the targetable mutations are there but they are somewhat not that common, I would say, in the 10-15% range. So many people would get dissuaded and then it's like, what's the point of doing it? But I think for those 10% to 15% of the patients, firstly we can really change their treatment course and their prognosis. Secondly, if you don't do it and they cannot go in a different clinical trials, now we have trials targeting KRAS G12C, but not only that, KRAS G12D which is the most common mutation we see in pancreatic cancer and so on. So it's becoming very very important. One thing, at least with our practice we adopted last two or three years is sending liquid biopsies or liquid based NGS or blood-based NGS testing. Otherwise, what's happening I would send a solid tumor NGS from the tissue. And pancreatic cancer as you know has sometimes a very small amount of tissue obtained from FNA. And inevitably after four weeks, we'll get the result that there's not enough tumor to do NGS testing. And then the patient comes one or two months later and then we order the test, and that just delays everything. So now we adopted a practice where we are trying to send both blood based NGS and solid tumor NGS at the same time the first time of diagnosis when we see the oncologist for the first time. And that has really increased the rate of NGS testing results for our patient population. And it's not 100%, even in blood-based NGS, sometimes they may not be able to find enough circulating tumor cells to do this blood-based NGS testing, but at least they're having these. But you're correct. I think we still see about one third of the patients who had not had NGS testing or referred for phase I clinical trial and have gone through more than two or three line of therapies which is unfortunate for our patients. Dr. Rafeh Naqash: That's a very interesting perspective on how important it is to sequence these individuals. As you said, it may not be that all of them may benefit, but the ones that have those important alterations, especially BRCA, PALB, and KRAS could benefit from novel precision medicine-based approaches. A question that came to my mind, I saw that you were trying to look at MYC and turmeric low tumors as well. So what is the role of MYC in the context of these individuals? Is there any drug development that's going on? Because I see small cell lung cancer. MYC is an important target there. These are two different tumors, but it looks like there was a hint of some correlation with respect to some of the findings that you showed. Is that something that you're currently looking at or planning to look at? Dr. Amit Mahipal: I think that if we just talk about MYC in general, it is present at somewhat lower rate. I think we found MYC amplification in about 5% or so of TMB-low patients who had that and not really seen in the TMB-high patients. So right now, I am not aware of any trials targeting MYC in pancreatic cancer. But as you said, if it's successful in lung cancer, maybe that's when we can transform into the pancreatic cancer group. Dr. Rafeh Naqash: Of course we can all learn from each other's specialties.We learned a lot from melanoma with respect to therapy. Hopefully, other fields can also benefit from each other's experiences in the space of drug development. Thank you so much for this interesting discussion. The last few questions are more or less about you as an individual researcher. So could you tell us briefly on your career trajectory and what led you into the space of GI oncology, pancreas cancer, even for that matter, drug development? And some of the advice that you may want to give to listeners who are trainees or early career individuals? Dr. Amit Mahipal: Sure. So I have gone through some different institutions. During my fellowship, that's when I really decided that I wanted to do GI oncology. Prior to that, I actually have a Masters in Public Health, where I learned about epidemiological research and how to design clinical trials, how to design cohort studies. My focus was on, actually there was somewhat a lot, but one of my mentors was working on colorectal cancer, and they had this huge database called the Iowa Women's Health Study Database of 100,000 patients. So that's where I started by clearly getting into colorectal cancer and GI cancer in general and how to learn from this database, how to mine these databases, how to do analyses, which seems easy but is actually quite complicated. During my fellowship, I think the key to it is finding a good mentor during the fellowship. And I worked with one of the top GI oncologists in the country who's practicing. And I worked under her and learned a lot not only from the clinic side but also from the research perspective and how sometimes you'll come up with the ideas during the clinic itself.Like, “Hey, this patient had this and why aren't we looking into this.” And she would even do some of the therapies based on phase II trials and she was a part of a lot of these trials and learning from those experiences. And following my fellowship, I joined Moffitt Cancer Center, where I led the phase I program there. So I was heavily involved in drug development programs, all training programs I've been to, NIH in Bethesda, an observership in the CTEP program, and also did the ASCO/AACR Vail workshop, where you really learned a lot in just like one week. So those are kind of opportunities present for fellows and even the early investigators and attendings as well in the first few years can go there, have your proposal. And really they are the world experts in trial design and they'll talk about how to design trials, how to add collaborators, improve your trial, and basically learn the whole protocol in a week so to speak. And then I was at Moffitt Cancer Center for about five, six years. My home was GI so I did both GI oncology as well as phase I. And in terms of the GI oncology, my main focus was pancreatic cancer and liver tumors. Then I was at Mayo Clinic in Rochester for about seven or so years. I kind of did the same thing and solidified my career at GI oncology, looking at liver tumors, and pancreatic cancer and then being a part of the phase I division program. And now, most recently, about a year or so ago, I joined Case Western to lead the GI program here. Dr. Rafeh Naqash: Are the winters in Cleveland better than the winters in Minnesota? Dr. Amit Mahipal: For sure. I always say, you don't know cold until you go to Minnesota. It's a different kind of cold. I'm sure people in Dakota might say the same thing, but the cold in Minnesota is very brutal and different compared to any other place I've been to. Dr. Rafeh Naqash: Well, it was great learning about you. Thank you so much for spending this time with us and for sharing your work with our journal. We hope you'll continue to do the same in the near future. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at ascopubs.org/podcasts. Dr. Amit Mahipal: Thank you for having me here, Rafeh. Good luck. Take care. Dr. Rafeh Naqash: Thank you so much. The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. The guests on this podcast express their own opinions, experiences, and conclusions. Their statements do not necessarily express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Mahipal: Consulting or Advisory Role:QED TherapeuticsAstraZeneca/MedImmuneTaiho Oncology Speakers' Bureau:AstraZeneca Research Funding:Taiho Pharmaceutical"

105: Matthew Rosenblum - Stage Four Pancreatic Cancer Survivor - Hazel Park, Michigan, USA

Oncology for the Inquisitive Mind

Play Episode Listen Later Dec 30, 2023 36:10

What began as an obstruction of Matthew Rosenblum's bile duct became a diagnosis of Stage Four pancreatic cancer, of which he learned via his cellphone. After two clashes with chemotherapy and two surgical procedures, Matthew leads a healthy lifestyle. Going forward, he wants to be an advocate for others diagnosed with pancreatic cancer. This is his story.

united states cancer survivors chemotherapy pancreatic cancer rosenblum stage four michigan usa hazel park gemcitabine folfirinox abraxane

CA19-9 Response to First-Line Neoadjuvant FOLFIRINOX and Second-Line Gemcitabine/Nab-Paclitaxel for Patients with Operable Pancreatic Cancer

Speaking of SurgOnc

Play Episode Listen Later Dec 12, 2023 15:33

Rick Greene, MD, discusses with Susan Tsai, MD, MHS, the results of an analysis examining the efficacy of second-line gemcitabine/nab-paclitaxel (GnP) after first-line FOLFIRINOX in the neoadjuvant setting among patients with operable pancreatic cancer who were treated with a total neoadjuvant approach. Dr. Tsai is the senior author of, “CA19-9 Response to First-line Neoadjuvant FOLFIRINOX and Second-line Gemcitabine/nab- Paclitaxel in Patients with Operable Pancreatic Cancer.” Dr. Tsai is Professor of Surgery and Chief of the Division of Surgical Oncology at The Ohio State University Comprehensive Cancer Center, Columbus, OH.

professor medicine chief patients md columbus surgery tsai pancreatic cancer mhs first line second line gnp surgical oncology neoadjuvant paclitaxel gemcitabine folfirinox ca19

74. ESMO 2023 - Upper GI and Hepatobiliary Cancer

Play Episode Listen Later Oct 30, 2023 24:48

Next up on the ESMO 2023 rollercoaster is an episode that is likely to be the shortest in our series: upper gastrointestinal and hepatobiliary oncology. As always, this remains a very challenging subarea of medical oncology, both in the clinical and trial spheres. However, our esteemed colleagues at ESMO remain undaunted by this challenge, and thus several studies of interest bear discussing. Will any of these studies lead to massive upheavals for clinicians and patients alike? For that answer, you'll have to listen on.Links to studies discussed in this episodes (subscription may be required):Tinengotinib in patients with advanced, fibroblast growth factor receptor (FGFR) inhibitor refractory/relapsed cholangiocarcinoma https://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/638034GEMSTONE-303: Prespecified progression-free survival (PFS) and overall survival (OS) final analyses of a phase III study of sugemalimab plus chemotherapy vs placebo plus chemotherapy in treatment-naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma https://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/639003Nab-paclitaxel plus gemcitabine versus modified FOLFIRINOX or S-IROX in metastatic or recurrent pancreatic cancer (JCOG1611, GENERATE): A multicentred, randomized, open-label, three-arm, phase II/III trial https://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/637982For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

cancer os acast gb complease pfs ii iii esmo upper gi music unlimited comart fgfr folfirinox

GI Cancer ASCO 2023 Highlights with Dr. Muhammad Shaalan Beg

Oncology Brothers

Play Episode Listen Later Jun 29, 2023 24:04

Discussing GI (Gastrointestinal) Cancer ASCO 2023 Highlights, focusing on practice-changing studies with Dr. Muhammad Shaalan Beg, Co-Leader Gastrointestinal Oncology, Adjunct Associate Professor of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center. Covering three important studies: - PROSPECT: ph III trial of neoad chemoRT vs neoadj FOLFOX chemo with selective use of chemoRT, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) - NORPACT-1: Short-course neoadj FOLFIRINOX vs upfront surgery for resectable pancreatic head cancer - NAPOLI 3: ph III trial in mets pancreatic ductal adenocarcinoma pts, liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) vs nab-paclitaxel + gemcitabine - IMbrave050: Efficacy, safety and patient-reported outcomes (PROs) from the phase III IMbrave050 trial of adj atezo + bev vs active surveillance in pts with HCC

university cancer pros covering prospect napoli internal medicine asco adjunct associate professor hcc texas southwestern medical center tme folfirinox folfox

Novel Therapies in GI Oncology at ASCO23

Play Episode Listen Later Jun 28, 2023 18:30

Drs. Shaalan Beg and Shiraj Sen discuss notable advances in GI cancers featured at the 2023 ASCO Annual Meeting, including the PROSPECT and PRODIGE-23 trials in rectal adenocarcinoma, the MORPHEUS study in uHCC, and the NORPACT-1 trial in pancreatic head cancer. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host for the podcast today. I'm the vice president of oncology at Science 37, and I'm an adjunct associate professor at UT Southwestern Medical Center. My guest today is Dr. Shiraj Sen. He is a GI medical oncologist and the director for clinical research at NEXT Oncology in Dallas. Today, we'll be discussing practice-changing studies and other key advances in GI cancers that were featured at the 2023 ASCO Annual Meeting. You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the podcast are available on our transcripts at asco.org/DNpod. Shiraj, it's great to have you on the podcast today. Dr. Shiraj Sen: Thanks so much for having me today, Shaalan. Dr. Shaalan Beg: We saw exciting new data and great progress in GI oncology at the ASCO Annual Meeting. I was hoping we could talk about LBA2. This was the PROSPECT study that was presented during the Plenary Session. It's a randomized, phase 3 trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemo, followed by the selective use of chemoradiation, followed by TME or total mesorectal excision for the treatment of locally advanced rectal cancer. This is the Alliance N1048 trial. What are your thoughts on this study? Dr. Shiraj Sen: Thanks, Shaalan. It was great to see another GI study presented in a Plenary Session, and I thought this was a great trial that really took us back to thinking about why we do chemoradiation as well as chemotherapy perioperatively in locally advanced rectal cancer. And asking the important question of is there a select patient set or subset where we might be able to safely omit the chemoradiation piece. To me, the impressive part was this study enrolled from 2012 to 2018. In 2012, when this treatment really started enrolling, the standard of care was long-course chemoradiation for five and a half weeks, followed by surgery, followed by adjuvant chemotherapy with FOLFOX or CAPOX. During this time, a lot of the practices of these patients have shifted from that to giving total neoadjuvant therapy, where we bunch the chemotherapy and chemotherapy upfront prior to the patient undergoing surgery. And this study really asked us to take a look at both practices and ask the question of which one is better and is it possible to de-escalate care for patients who get upfront chemotherapy and omit the chemoradiation and still have similar outcomes. I thought it was very interesting that this was done in a non-inferiority-type manner, and we can talk more about that in a few minutes as well. But taking that all into context, the fact that in this study, that the non-inferiority endpoints were met for both disease-free survival as well as overall survival in the patients who were able to omit chemoradiation, I think in the big picture sense told us that there truly might be a patient subset where—this is in patients with T2 node-negative disease or T3 node-negative or T3 node-positive disease—where we might be able to safely exclude the chemoradiation and still have similarly effective outcomes for these patients. Dr. Shaalan Beg: Those are great points, especially when we have started to think about colon cancer and rectal cancer as many different diseases based on their location. And we know that in some instances their biology can be different as well. Can you talk a little bit about who those patients are that were enrolled on this trial? Because when I think about the German rectal study that led to us using neoadjuvant chemoradiation, the data was really around pelvic control of disease and sphincter preservation. So how did the patients who enrolled in this trial relate to the typical person with rectal cancer who walks through your doors? Dr. Shiraj Sen: Yeah, great point. I think we should point out the inclusion-exclusion criteria for this study. These patients were only those who were, again, T2 node-positive or T3 node-positive or negative, patients for whom chemoradiation would be indicated in the setting, and patients for whom they'd be good candidates for sphincter-sparing surgeries. So, tumors that are quite up high. These are not for individuals who have tumors requiring an APR. These are not for patients who have clinical T4 tumors. And this is not applied, again, to those high-risk patients who have 4 or more pelvic lymph nodes that are 1 cm in size or larger in the short access. And so, patients who need essentially an APR and the high-risk T4 tumors who are, I think, better suited by something like we'll talk about later in the PRODIGE study. I think one last point that might be worth making here on the PROSPECT trial is that it was a non-inferiority trial. And in my opinion, this was really a great use of a non-inferiority study. I believe that when there's a new treatment under consideration used in a non-inferiority study, it should be because that therapy or modality of treatment is safer, more cost-effective, or could help increase access to care without compromising efficacy, and ideally maybe more than one of the above. And in this case, I think really all of those checkboxes are met. In urban settings where we work, we think about access to radiation being quite plentiful, but when we get to more rural areas, or parts of the world where they may not have access to radiation like we may, I think this data can help drive care for a number of patients there. It can certainly be more cost-effective as it allows the omission of radiation. And certainly, from some of the PRO data that they presented, it certainly can be felt to be safer and help omit some toxicities as well. Dr. Shaalan Beg: Yeah, you mentioned a total neoadjuvant therapy and we seem to be entering this space in rectal cancer where the decision on which modalities an individual person will need for the management of their disease and what sequence they will need is all up for debate, whether that's chemotherapy or radiation, long-form, short-form radiation. And we also heard some results at earlier ASCO meetings around the omission of surgery in people who've had complete clinical responses as well. And you mentioned total neoadjuvant therapy and at ASCO this year we heard the results from LBA3504, which is a PRODIGE-23 trial. The investigators reported 7-year results of this phase 3 study from the UNICANCER group in France. This study is really pushing the envelope. What are your key takeaways here? Dr. Shiraj Sen: Great point. I think this study, especially when taken in conjunction with the PROSPECT trial, highlights the fact that these patients really can have heterogeneous diseases and ones that really require careful consideration and discussion at multidisciplinary tumor boards. Unlike the patient population in the PROSPECT trial, the PRODIGE study did treat patients with higher-risk disease. So these were patients with clinical T3, T4 tumors and so higher risk, and asked the question now with more mature 7-year follow-up of, when compared to receiving the standard of care at the time, which was a chemoradiation followed by TME, followed by adjuvant FOLFOX for 12 cycles or the capecitabine, does TNT giving again now modified full FOLFIRINOX for six cycles followed by chemoradiation followed by TME and then adjuvant FOLFOX, do the improvements in both disease-free survival, overall survival, and metastatic relapse rate, do they hold up, and/or are there any differences in local control? And again, here they demonstrate that even with longer-term follow-up, that the improvements in OFS, DFS, and metastatic relapse rate, really do hold up even with longer-term follow-up. And so, for these patients with higher risk disease, it does seem that giving induction chemotherapy with modified FOLFIRINOX before chemoradiotherapy really might be kind of best practices. The safety profile, even with longer-term follow-up was unchanged. There was not any increase in local recurrences. And again, looking at quality of life metrics there seemed to be similar or maybe improved quality of life for patients who receive the TNT approach. And now again, I think the next step is, as the presenter mentioned, investigating this even in a more tailored fashion, as was done with the PROSPECT study. Dr. Shaalan Beg: Let's change gears and talk about liver cancer. Abstract 4010 showed the results of the MORPHEUS-liver study. This was a phase 1b/2 randomized trial of tiragolumab in combination with atezolizumab and bevacizumab for people with unresectable locally advanced or metastatic hepatocellular cancer. It's really exciting to see innovations with immune therapy changing how we've managed hepatocellular cancer in the last few years. And here, we're seeing an addition of a third agent to an already approved regimen of atezolizumab and bevacizumab. I was really curious to hear what your take-home message is from this study. Dr. Shiraj Sen: Yeah, this was another very interesting abstract that was presented at ASCO this year. It's hard to believe that it was only 3 years ago that we first got the approval of atezo plus bev, and that it took more than a decade to really have us as a field improve on outcomes for patients with liver cancer above and beyond giving sorafenib. And here we are just 3 years later, already launching new phase 3 studies from these sorts of early-phase adaptive signal-seeking studies. The investigators as a whole should be commended for the speed at which new drug development has really progressed in liver cancers after, again, quite a lull we had in the pre-I/O days. It's encouraging to see that in just 3 years that there's another phase 3 study now being launched in HCC on the heels of this data combining the atezo-bev backbone to the anti-TIGIT molecule tiragolumab. Now, I know there was a lot of discussion and some criticism of this study and what the real effects of adding tiragolumab to atezo-bev might be because of the underperformance of the control arm. In this study, the atezo-bev control arm, it should be noted that was only 18 patients, had a response rate of only 11%. And of course, with longer-term follow-up of the IMbrave150 study, we know that with the atezo-bev, we expect a response rate of about 30%. And so how a real-world population of individuals receiving atezo-bev would compare to those receiving tiro-atezo-bev has been discussed. But I think the only real way to answer that question would be with a large, randomized phase III study. And it's encouraging to see that one is being launched to ask that question. Dr. Shaalan Beg: Absolutely. Let's change gears and talk about pancreatic cancer. LBA4005 explored short-course neoadjuvant FOLFIRINOX versus upfront surgery for people with resectable pancreatic head adenocarcinoma in the NORPACT-1 study. This is a multicenter randomized phase 2 trial and we're starting to see the reporting of clinical trials evaluating the sequencing of systemic therapies for resectable disease. We've heard studies for neoadjuvant therapy for borderline resectable as well as resectable trials in previous meetings. But there's a lot of discussion around the NORPACT-1 trial which may be causing some people to pause on our current understanding of treatment sequencing for resectable disease. I'm curious to hear what your take homes are. Dr. Shiraj Sen: Thanks. Yes, I thought this was a very interesting study as well. Depending on which institution one practices in, in recent years, many have shifted their practice for individuals with resectable pancreatic cancer from administering full FOLFIRINOX or adjuvant therapy only after surgery to giving it in the neoadjuvant setting based on, again, a number of smaller studies, some that are single institution. This is one of the first studies that in a randomized fashion has asked the question in just resectable pancreatic cancer. So we're not talking about borderline resectable or other patients. But in resectable pancreatic cancer, whether there are differences now comes if patients receive surgery first, followed by FOLFIRINOX-only adjuvant setting or essentially getting perioperative FOLFIRINOX and so neoadjuvant, followed by surgery, followed by, as tolerated, four cycles of adjuvant FOLFIRINOX. And I was a little surprised by some of the results and to me some of these data were a little intriguing. Specifically, I think if we take a deeper look like the discussant had after the presentation, there are, I think, some unanswered questions. Specifically, half the patients were randomized to receive neoadjuvant FOLFIRINOX and half of them received upfront surgery. But in the group of individuals who received neoadjuvant FOLFIRINOX, it looked like only half of them completed neoadjuvant chemotherapy. And some answers into kind of why that was, and what it was about those patients then who were in the neoadjuvant arm, is one thing that comes to mind. Secondly, what I thought was interesting was this study was that it was designed very well to try to take out as much heterogeneity as possible. However, in both arms, there was actually quite a substantial number of individuals who ended up receiving gemcitabine-based chemotherapy. And that's even in the patients who received neoadjuvant FOLFIRINOX, and individuals who received neoadjuvant FOLFIRINOX, only 25% post-op went on to receive adjuvant FOLFIRINOX. And 75% almost received gemcitabine-based therapy. And again, why so many patients received off-protocol adjuvant therapy is something that kind of struck me. I think the third and final thing that really struck me was, in the patients that received neoadjuvant FOLFIRINOX, there was a higher rate of R0 resections. 56% of patients had an R0 resection compared to those who got upfront surgery, where there was only a 39% rate and similarly kind of higher levels of N0 resection. And yet, despite all of this, again, the authors did show quite clearly that there were not any significant improvements in outcomes for patients that received neoadjuvant therapy, but kind of how improved surgical endpoints do not translate to overall survival and overall endpoints; I think there are still some questions there. However, I do agree overall that despite these limitations with the conclusions of the author, that at this time at least, it's not clear; the results don't support the widespread use of neoadjuvant FOLFIRINOX as a standard of care for resectable pancreatic cancer. Fortunately, there are studies ongoing, like the Alliance [for Clinical Trials in Oncology] study and the PREOPANC-3 study that hopefully will kind of help settle this verdict. Dr. Shaalan Beg: Yeah, it's a stark reminder that we need better treatments. I think we've been shifting the sequencing of these treatments and slicing them in as many ways as we can. And the core challenge is in finding better systemic therapies that have been found to be effective in advanced stage as well as in curative stages like this. And one of the points that bothered me about this trial was the drop-off that they saw at the beginning when the biliary system was being drained, or they were getting biopsies because folks who went for surgery upfront didn't always require those procedures. They didn't require histologic diagnosis either. But as is standard practice, before we give systemic therapy, we require psychologic confirmation. And that may have introduced a delay of a couple of days or a couple of weeks, which could have resulted in some imbalances in how survival is measured and how folks were doing. Because, as you know, a lot of times people diagnosed with this disease can be fairly sick, and a matter of a couple of days or weeks can make a big difference in terms of treatment with those. I'm really excited to wait and hear how the Alliance study and the PREOPANC follow-up trials pan out and as a very important cautionary note for everyone, both the folks who have adopted neoadjuvant therapy and those that have not followed the data. And kudos to the investigators for completing that trial. Dr. Shiraj Sen: Yeah, I fully agree. I'm glad to see that these trials are being run. I think we should not take anything away from the fact that these are very challenging trials to run. I think we certainly owe a big kudos to the patients who enroll in these studies who have resectable disease, but they're still willing to go through the process of an extra consent form, an extra kind of screening process, additional testing required to go into a clinical trial. And it's only because of them that we're able to run these studies and, as a field, get some answers on how to best take care of our patients. Dr. Shaalan Beg: Shiraj, thank you so much for coming to the podcast today and sharing your valuable insights on the ASCO Daily News Podcast. Dr. Shiraj Sen: Thank you so much for having me, and to all of the ASCO staff for having this podcast. 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. 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 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. Shiraj Sen @ShirajSenMDPhD   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. Shiraj Sen: Employment: Roche/Genentech Stock and Other Ownership Interests: Roche/Genentech Research Funding (Institution): ABM Therapeutics, Zentalis Pharmaceuticals, Parthenon Therapeutics, Pyxis Oncology, Georgiamune Inc.  

science france german alliance depending gi prospect drs tnt io abstract oncology clinical trials merck dfs t2 morpheus t3 t4 asco hcc ut southwestern medical center prodige ofs tme r0 plenary session novel therapies asco annual meeting foundation medicine folfirinox tigit folfox merck serono capox astrazeneca medimmune

Meet The Professor: Optimizing the Management of Colorectal Cancer — Part 3 of a 3-Part Series

Oncology for the Inquisitive Mind

Play Episode Listen Later Jun 8, 2023 58:27

Featuring perspectives from Dr Michael J Overman, including the following topics: Introduction (0:00) Case: A woman in her mid 40s with microsatellite instability-high (MSI-H) colorectal adenocarcinoma metastatic to the brain receives pembrolizumab; KRAS G13D and somatic BRCA exon 11 mutations — Warren S Brenner, MD (16:27) Case: A woman in her late 50s with MSI-H Stage IIIB adenocarcinoma of the colon, BRAF V600E mutation — Eric H Lee, MD, PhD (23:20) Case: A woman in her early 70s with past medical history of diverticulitis and partial colectomy diagnosed with T1, microsatellite stable (MSS) cecal colon adenocarcinoma, minimum residual disease-negative after resection — Farshid Dayyani, MD, PhD (32:37) Case: A woman in her late 60s with past medical history of hypothyroidism has mass in right lung consistent with colorectal adenocarcinoma but no evidence of primary or other distant disease — Swati Vishwanathan, MD (42:58) Case: A woman in her mid 60s with multiregimen-relapsed RAS wild-type, HER2-positive metastatic rectal cancer, now receiving trastuzumab/tucatinib — Sunil Gandhi, MD (46:51) Case: A man in his mid 60s with MSS metastatic cecal adenocarcinoma and progressive disease on FOLFIRINOX/bevacizumab and capecitabine/bevacizumab maintenance — Dr Brenner (50:13) Case: A woman in her mid 60s with metastatic BRAF V600E-mutant colorectal adenocarcinoma, with circulating tumor DNA positivity after FOLFOX, heated intraperitoneal chemotherapy and colectomy/debulking surgery — Jeremy Lorber, MD (54:31) CME information and select publications

phd professor management dna md optimizing ras brenner cme colorectal cancer t1 brca her2 mss braf v600e folfirinox msi h folfox michael j overman

42. ASCO 2023 - Gastroesophageal, Pancreatic and Hepatobiliary update

Play Episode Listen Later Jun 4, 2023 30:05

ASCO 23 (American Society of Clinical Oncology) Annual Meeting in Chicago showcased a plethora of cutting-edge trials and research. Upper gastrointestinal cancers such as gastric, pancreatic and hepatobiliary are usually relegated to the backstage, but this year, several exciting and potentially practice-changing studies (not without their limitations).We explore a new PD-1Toripalimab in gastric and gastroesophageal cancer, liposomal irinotecan in NALIRIFOX versus gemcitabine/abraxane in metastatic pancreatic cancer, neoadjuvant FOLFIRINOX in pancreatic cancer and the new HER2 kid on the block zanidatamab, a bispecific monoclonal antibody.Stay tuned for daily ASCO updates from the OFTIM team, Michael and Josh.Studies:Toripalimab + SOX study: https://meetings.asco.org/abstracts-presentations/219777NAPOLI-3 study: https://meetings.asco.org/abstracts-presentations/222090NORPACT-1 study: https://meetings.asco.org/abstracts-presentations/219426HORIZON-BTC-01 study: https://meetings.asco.org/abstracts-presentations/219904Special Mention (not included in the episode)DIPLOMA Study: https://meetings.asco.org/abstracts-presentations/218312Lauren Classification: https://open.acast.com/shows/62d20dbcffef490011c8df4b/episodesMany thanks to Merck for supporting this episode. Merck provided virtual access to ASCO 2023 but did not review or approve any part of OftiM's coverage of ASCO.For more episodes, resources and blog posts, visit www.inquisitiveonc.comFind us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

chicago acast american society upper merck asco pancreatic her2 gastroesophageal music unlimited comart folfirinox

ASCO23: CodeBreak-101, NAPOLI-3, and Other Advances in GI Cancers

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later May 25, 2023 21:45

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

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JCO Article Insights: Use of Independently-Assessed vs Investigator-Assessed DFS in the APACT Trial

Play Episode Listen Later May 15, 2023 14:26

In this JCO Article Insights episode, Emily Zabor interviews Dr. Gulam Manji from Columbia University Irving Medical Center. Dr. Manji provides insight into his editorial published in the April 10, 2023 JCO issue: "Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence?” (10.1200/JCO.23.00039). His editorial focuses on the JCO Original Report, “Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial” by Tempero, et al on the APACT Trial. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Emily Zabor: Welcome to this JCO Article Insights episode for the April issue of JCO. This is Emily Zabor, one of JCO's editorial fellows. And today I am interviewing Dr. Manji from Columbia University on their editorial titled “Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence?” Dr. Manji, welcome to our podcast. You wrote this editorial to accompany the article, “Adjuvant Nab-Paclitaxel plus Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results from a Randomized Open-label Phase III Trial by Dr. Margaret Tempero and Colleagues.” That trial, called the APACT Trial, investigated the efficacy and safety of adjuvant nab-paclitaxel plus gemcitabine compared to gemcitabine alone in patients who had undergone resection for pancreatic ductal adenocarcinoma. So I wanted to ask if you could start by giving listeners a quick overview of the study design and the main findings from that trial. Dr. Gulam Manji: Yeah, sure, Emily. So, as you pointed out, it was a randomized phase III study in patients who had resected pancreatic carcinoma. The primary endpoint was independently assessed disease-free survival. Additional endpoints included investigator-assessed disease-free survival, overall survival, and safety. And we'll get back later on as far as the importance of investigator-assessed versus independently-assessed disease with survival because I think that that's the main point of discussion for today. The enrollment criteria were fairly stringent and included patients with macroscopic complete resection, ECOG performance status of either 0 or 1, and the peripheral tumor markers of CA 19-9 being less than 100. And patients were required to initiate adjuvant chemotherapy within 12 weeks. Patients received standard gemcitabine at 1000 milligrams per meter square, either with or without nab-paclitaxel of 125 milligrams per meter square once weekly for three weeks during every four-week cycle. Emily Zabor: Great. So I think that the main thing that we wanted to talk about today, and one of the main points you discuss in your editorial is the difference between the primary endpoint of independently assessed disease-free survival and the secondary endpoint of investigator-assessed disease-free survival. So can you describe the difference between those endpoints, how they were defined, and how they differed? Dr. Gulam Manji: Sure. So, independently-assessed DFS was determined by a radiologist who was blinded to treatment assignment, and new lesions followed RECIST 1.1 criteria. In contrast, the investigator-assessed recurrence was determined by the treating physicians using all available clinical information. So that could be abdominal pain, anorexia, probably elevation of peripheral tumor markers. And the other important aspect to the study is that the independent review was not performed in real-time to confirm investigator assessments. So patients who started subsequent therapy after recurrence by treating investigators were censured for the independently-assessed DFS analysis. So in this trial, 866 patients were randomized. And patients who are randomized to the experimental arm had a median independently assessed DFS of 19.4 months, while patients randomized to the control arm, which was gemcitabine alone, had a median DFS of 18.8 months. Now, when we compare that to the investigator-assessed DFS, the data looks quite different. Where the DFS was 16.6 months in the experimental arm compared to 13.7 months in the control arm. That is consistent with the five-year follow-up looking at the median overall survival, which was 41.8 months for the combination arm compared to 37.7 months for the gemcitabine alone arm. Emily Zabor: Okay, so there's some really interesting differences there. And I noticed that there were only 439 events according to the independently-assessed DFS versus 571 according to the investigator-assessed DFS. So that's a big difference in the number of events that I guess is coming from that additional censoring that was occurring due to the delay in the independently assessed endpoint. Is that right? Dr. Gulam Manji: Exactly. So you could envision a scenario where patients received chemotherapy and then on the investigator-assessed DFS, the investigators decided that the patient had recurred. However, that patient probably did not meet the RECIST or radiological criteria to determine that that patient had recurred. And hence, since it was not done in real-time, there was censoring that occurred for the independently-assessed DFS. So that's the reason why there was a difference in that number as you pointed out. The decision to use independent DFS, disease-free survival, really was to remove investigator-associated bias and increase rigor to the study, which is commendable. However, unfortunately, that's not how we normally treat patients with aggressive cancer who have undergone surgical reception. And knowing that imaging modality is limited in identifying those patients, particularly in those that have peritoneal disease, or even more importantly, the patients who have recurrence within the surgical bed, I think is the issue. Emily Zabor: Right. So the motivation behind selecting that endpoint was really good and well-motivated. Everybody wants to reduce bias and make sure we're taking out those kind of more subjective parts of identifying that. But it, unfortunately, missed some events as a result. Dr. Gulam Manji: Correct. I think that it delayed those events and that's what compromised the analysis because it was the limitations of the available modalities to determine when recurrence occurs. Emily Zabor: So how do these different definitions compare to other trials or previous trials? Dr. Gulam Manji: So previous trials that I'm aware of, it was the investigator-assessed DFS that had been used. And when you look at the data that was used in this trial, that concurs with what has historically been seen. And what I mean by that is that the original assumptions regarding DFS when this trial was being designed, used historical outcomes. Investigators see that DFS with adjuvant gemcitabine ranged anywhere from between 13.4 to 14.3 months. And the study had aimed to achieve a DFS improvement from 13.5 to 18.5 months. When you look at the investigator-assessed DFS, the ballpark of gemcitabine is very much in line with the previous historical data. So I think that the key discrepancy between the two DFS endpoints was likely a delay in accurately assessing disease recurrence when using the blinded radiological modality alone. And the second thing is, as you pointed out, a greater proportion of patients who were censored for independent assessments compared with those for investigator assessments was different. So that was between 40% versus 34%. So those two points, I think, were the key points that show the difference between independent versus investigator-assessed DFS and also that the independent-assessed DFS was not done in real-time. Emily Zabor: Yeah, that's really interesting and such a good point. And I think it really emphasizes how important it is to think carefully about these endpoint definitions in the design stage of these clinical trials and especially to think about when and why patients are getting censored and how that might impact the results. So how do these results of this trial then, given the negative result of the primary endpoint, but that positive result on the secondary investigator-assessed endpoint, how do these fit in with other trials? And what do you think that means for patient treatment recommendations? Dr. Gulam Manji: Excellent point. So just to be clear, the APACT study did fail to meet its primary endpoint and hence gemcitabine and nab-paclitaxel were not indicated for patients in the adjuvant setting. The current standard of care are either modified FOLFIRINOX or gemcitabine combination with capecitabine. And those two regimens really remain a standard of care for patients. So what I do is for fit patients, I prefer modified FOLFIRINOX. However, in patients who are not as fit, gemcitabine in combination with capecitabine is the alternative. Now, one could envision a scenario where gemcitabine and nab-paclitaxel may become relevant. It is, but only when I'm really pushed to do so, where I feel like there is no other regimen available optimally for a patient. And one could envision a scenario where you could have a patient who does not have the performance status to tolerate modified FOLFIRINOX and then you start that patient on gemcitabine in combination with capecitabine. However, I have experienced that that combination results in significant myelosuppression in patients in the United States. And then we have to do significant dose reductions or interruptions. Now, in that case, where I feel like I'm reducing the dose of capecitabine to a point where the patient may not be potentially benefiting from that regimen, it's impossible to determine what dose would be efficacious when you're doing those dose reductions. That is the only scenario where I may be able to be pushed to consider gemcitabine and nab-paclitaxel, but only after also discussing with the patient the results of the current data and there being limited efficacy. Emily Zabor: That makes sense. So the treatment you would select would really depend on some patient characteristics and then how they do on the different treatments. Dr. Gulam Manji: Correct. Emily Zabor: So what do you think are the next steps for research in this area and in this disease? Dr. Gulam Manji: I think that this clinical trial really demonstrated our inability to accurately pinpoint the time of disease recurrence using imaging modalities alone. And for patients who treat pancreas cancer, they would know that the recurrence patterns usually are either to the liver or to the peritoneum, or to the lung. However, in about 25% of the cases, the recurrence may be at the surgical site, and that's when things become tricky. After patients have undergone surgery, their scar tissue and the pancreas tumor is very dense, so it's difficult to determine that there's actually tumor growth. So that's where you really need help from other modalities. So should we get a PET scan? Is the patient symptomatic? Is a tumor marker going up in the absence of biliary obstruction? So all of those things need to be taken into account to truly pinpoint whether the patient has recurred or not. In peritoneal disease, you may need to ask the surgeons to help and have the patient undergo a laparoscopy to truly determine whether there is a peritoneal disease. And lastly, I think that incorporating ctDNA to better define whether there is a minimal residual disease will likely be a standard in the future. Emily Zabor: I see. Yeah, that makes sense. Incorporating some ctDNA biomarker information along with these really detailed clinical and possibly imaging assessments to determine recurrence seems like it would be really important in future trials to make sure you're capturing all of those recurrences accurately. Dr. Gulam Manji: Yeah, I think that that's critical before you can say that an adjuvant treatment is truly helping the patient. Emily Zabor: That's great. Well, I really learned a lot reading this article and speaking to you today. But before we end, is there anything else you'd like to share with our listeners? Dr. Gulam Manji: Yeah, so I think we know that for a majority of patients who undergo curative resection, unfortunately, the disease recurs. And I think that that implies that, really, pancreas cancer is a systemic disease at the time of diagnosis. And despite aggressive adjuvant therapy, the median DFS, OS, and five-year survival rate show that we are impacting only a subset of patients with six additional months of chemotherapy. So I think that identifying predictive markers of response to systemic therapy, better selection of patients for surgery, perhaps using total upfront neoadjuvant therapy, an institution of maintenance therapy, and patients who are at high risk for recurrence, perhaps using ctDNA as a marker to determine who those high-risk patients are, all leads to help better design and identify patients who should really be treated systemically and patients who should undergo surgery. And lastly, with some glimmers of success from personalized vaccines may be on the horizon. And I'm hoping in the near future to treat minimal residual disease so that we can get the best outcome with minimal toxicity for our patients. Emily Zabor: That's great. That sounds like an exciting development for a disease that seems really tricky. Dr. Gulam Manji: Agreed. Emily Zabor: Well, thank you so much. It has been a pleasure speaking with you, Dr. Manji, and thank you so much for joining me today on this episode of JCO Article Insights. This concludes the episode on the article “Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence?” Thank you for listening and please tune in for the next issue of JCO Article Insights. 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. Show Notes: Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr. Gulam Manji, MD, PhD is a medical oncologist at the Columbia University Irving Medical Center in New York. Articles: Editorial: Adjuvant Gemcitabine and Nab-Paclitaxel Misses the Target in Pancreas Adenocarcinoma: Or Did an Effective Therapy Fall to the Definition of Recurrence? Original Report: Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial Find more articles from the April 10 issue.

Paula Ghaneh on the ESPAC5 trial of neoadjuvant therapy in borderline resectable pancreatic cancer

In conversation with...

Play Episode Listen Later Jan 23, 2023 20:20

Paula Ghaneh (University of Liverpool) discusses the ESPAC5 randomised controlled trial of short-course neoadjuvant therapy compared with immediate surgery for patients with borderline resectable pancreatic ductal adenocarcinoma. Read the full article:Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5)Continue this conversation on social!Follow us today at...https://twitter.com/thelancethttps://instagram.com/thelancetgrouphttps://facebook.com/thelancetmedicaljournalhttps://linkedIn.com/company/the-lancethttps://youtube.com/thelancettv

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Die Totale neoadjuvante Radiochemotherapie (TNT)

Podcast Viszeralmedizin

Play Episode Listen Later Aug 19, 2022 26:45

In unserer neuen Folge sprechen wir im schönen Greifswald über die Totale neoadjuvante Radiochemotherapie (TNT). Diesbezüglich haben wir uns die PRODIGE 23-Studie genau angeguckt und diese in den wissenschaftlichen Kontext gestellt. Viel Spaß Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715.

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Episode 214 - Surviving with Kit Rudd

Project Purple Podcast

Play Episode Listen Later Aug 12, 2022 73:52

This week, we're joined by Kit Rudd, a pancreatic cancer survivor who was originally from Texas and now lives in Richmond, VA. Kit is a rockstar survivor who is geared towards helping others through a variety of fundraisers that mainly focus on cycling and competitive cooking! In this episode, Kit details his journey from symptoms to present-day. He also tells some interesting stories dating back before his symptoms including the time he had the pleasure of flying Alex Trebek during his days as an Air Force Pilot. Through familial & friendship connections and a number of other threads including his own name, Kit has had ties to pancreatic cancer since long before he began his personal battle. And today he is extremely dedicated to fighting back against this disease - even while undergoing treatment with FOLFIRINOX. If you're interested in helping Kit fundraise for Project Purple, you can buy a Pancannibals cycling jersey here: https://www.journeymans.co/kits-pancannibals-fundraising-club-jersey.html To follow along with Kit's journey, follow him on Instagram and on Facebook at these links: https://www.instagram.com/cookinupacure https://www.facebook.com/kit.rudd.5 To learn more about Project Purple, visit https://www.projectpurple.org/ or follow us on social media at these links: https://www.facebook.com/Run4ProjectPurple https://www.instagram.com/projectpurple/ https://twitter.com/Run4Purple https://www.youtube.com/channel/UCgA8nVhUY6_MLj5z3rnDQZQ

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Novel Therapies in GI Oncology at ASCO22

Play Episode Listen Later Jun 27, 2022 15:31

Dr. Rachna Shroff, of the University of Arizona Cancer Center, tells guest host, Dr. Shaalan Beg, of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Science 37, about advances in precision medicine for pancreatic cancer featured at the 2022 ASCO Annual Meeting. She also highlights compelling new data from the FOLFOX, FOENIX-CCA2, and HERB trials in hepatocellular carcinoma, cholangiocarcinoma, and biliary tract cancer. TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Shaalan Beg, your guest host of the ASCO Daily News podcast today. I'm an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. I'm delighted to welcome Dr. Rachna Shroff, the associate dean for clinical and translational research and the chief of gastrointestinal (GI) medical oncology at the University of Arizona Cancer Center where she's also the interim chief of Hematology-Oncology. Dr. Shroff is also the chair-elect for the Gastrointestinal Cancer Symposium. Today we'll be discussing key abstracts in GI cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all our guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Shroff, thank you for being on the podcast today. Dr. Rachna Shroff: Thank you so much for having me. Dr. Shaalan Beg: Let's begin by reviewing what is new in the realm of precision medicine in GI cancers. One of the diseases where precision medicine has not made adequate inroads is pancreatic cancer. One of the most common mutations in pancreas cancer is KRAS, but there haven't been a lot of treatments that can target the most common forms of KRAS. What did we hear at ASCO22 regarding precision medicine and pancreatic cancer? Dr. Rachna Shroff: I agree, I think that the area of precision oncology is, unfortunately, lagging behind a little bit in pancreatic cancer. But I think as we have gotten better and better with our comprehensive genomic profiling, we are identifying subsets of patients within pancreas cancer who are potentially amenable to targeted therapies. You already mentioned KRAS mutations, and we obviously have a number of inhibitors in development in that space, though, we are still missing that key G12D mutation that we see in pancreas cancer. But what I think was really interesting that came out of ASCO22, was a lot of interest and emphasis on better understanding the KRAS wild-type patients in pancreatic cancer. Now, this is obviously a smaller subset of patients, given that the majority of patients have KRAS mutations. But there was a really interesting abstract, LBA4011, that looked at patients with locally advanced or metastatic pancreatic cancer, who were KRAS wild-type. They actually received gemcitabine in combination with a monoclonal antibody targeting EGFR and nimotuzumab. This was a study that was done entirely in Asia. It involved 92 Chinese patients that were randomly assigned to receive the combination of nimotuzumab with gemcitabine. What was interesting in this study is that the patients were found in the full analysis set to have a significantly longer median overall survival of 10.9 months versus 8.5 months with a hazard ratio of 0.5. So, that of course was intriguing and provocative for sure. Similarly, the other endpoints were also somewhat intriguing in terms of improvements in the median progression-free survival (PFS), etc. And specifically, patients without biliary obstruction had a longer PFS, which was an interesting finding as well. The nimotuzumab overall was pretty well tolerated and not any sort of surprising treatment-related adverse events (TRAEs) were noted. And so, this is definitely a drug that, I think, piques our interest in terms of being able to target patients with KRAS wild-type pancreatic cancer. I think that questions, however, that remain, and I think require further study is really understanding what this drug could do in combination with the chemotherapy combinations that we use more frequently in metastatic pancreatic cancers such as gemcitabine and paclitaxel or 5FU-based regimens like FOLFIRINOX. I think given that it is a relatively well-tolerated drug, it would be a very reasonable thing to investigate this drug further in the KRAS wild-type population with the kind of modern-day chemotherapy regimens that we use. And I think, of course, we all know that it is useful to be able to look at these types of drugs in a more global population. And so, a larger patient set I think would be very useful as well, but at least it tells us that there is a way to think about our KRAS wild-type patients with pancreas cancer and that perhaps we really need to understand and identify those patients' potential for precision oncology. Dr. Shaalan Beg: One of the GI cancers that has been a hotbed for precision medicine is cholangiocarcinoma, a disease that's very close to your heart. What updates did we hear at ASCO22 regarding cholangiocarcinoma and precision medicine? Dr. Rachna Shroff: This space of targeted therapy and cholangiocarcinoma has been incredibly exciting for the last few years and I think drug development has been rapid-fire in that space. The oldest, if you will, target that we've been thinking about for some time is the FGFR2 fusion patient population. And in Abstract 4009 by Dr. Goyal and colleagues, we saw the results of the FOENIX-CCA 2 trial which was looking at an oral FGFR inhibitor (futibatinib) in patients with intrahepatic cholangiocarcinoma, who harbor FGFR2 fusions and gene rearrangements. We had initially seen some of this data presented a few years back, but this was the updated data set. It was a single-arm phase 2 study that involved patients with advanced intrahepatic cholangiocarcinoma who had identified FGFR2 gene fusions, and they received futibatinib daily until progression. This was a traditional single-arm phase 2 study with a primary endpoint of overall response rate. At the final data cut, with a median follow-up of 25 months, there's actually a confirmed overall response rate of 41.7%. And I think that what was really exciting about this is this is a refractory patient population. So, in patients who have refractory cholangiocarcinoma, the other drugs, the non-targeted therapy drugs that we think through, really have response rates more in the single-digit to 10% range and so to have a confirmed overall response (OR) over 40% is truly exciting. The duration of the response was also exciting. This is not just a drug that works briefly, it has a duration of response of 9.5 months. And the mature median overall survival was 20 months. And in a disease which we talk about with the ABC-02 data of GemCis, a median OS in advanced disease of 11.7 months. This is really, really exciting for patients who harbor this fusion or gene rearrangement. We know that that's seen in about 10 to 15% of patients. So, again, we're dealing with a smaller subset, but it clearly demonstrates the need to identify FGFR2 gene fusions, so that we can offer these types of targeted therapies. This was not the first FGFR inhibitor that we have seen data on and in fact, we have 2 drugs already U.S. Food and Drug Administration (FDA) approved. And so, when we look at the common treatment-related adverse events that were identified with the futibatinib, there are really class effects related to FGFR inhibition like hyperphosphatemia, alopecia, dry mouth, nothing that really stood out or that was concerning. And so, I think this final analysis for the FOENIX study really just reaffirms the utility of futibatinib in patients with FGFR2 gene fusions, and the mature OS data, the duration of response, all of this really aligns with the need to identify patients with this alteration so that we can, post-gemcitabine based therapies, offer this targeted therapy or an FGFR inhibitor in general to these patients. I think the other really exciting abstract in the glandular carcinoma or biliary tract cancer space was Abstract 4006. This was the updated data from the HERB trial, which was an investigator-initiated multicenter phase 2 trial looking at trastuzumab deruxtecan (T-DXd) in patients who have HER2 expressing unresectable or recurrent biliary tract cancer. Trastuzumab deruxtecan, I'm sure everybody has been hearing about because it has been incredibly effective in HER2 alterations across a myriad of different disease sites. And so, not wanting to be left out, biliary tract cancers were investigated in this study with patients who had HER2 expression, so, that was HER2-positive IHC3+ or IHC2+/ISH+, and they also looked at HER2-low expressing patients, and [whose disease] were refractory or intolerant to gemcitabine-based therapy with the primary endpoint of overall response rate. So, in the HERB trial, a total of 32 patients were enrolled. 24 of them were HER2-positive and 8 were HER2-low and they all received trastuzumab deruxtecan. When you look at the efficacy data, the confirmed overall response rate in the patients with HER2-positive was 36.4%, which again, as I said, in a refractory patient population is certainly very exciting data. And the overall disease control median, PFS, and median OS were all pretty encouraging in terms of efficacy. What was also kind of intriguing was that there was some efficacy seen even in the patients who are HER2-low. Now, this is, in my opinion, a slightly less exciting amount of efficacy, but still important to note that the overall response rate in HER2-low was 12.5% with a median PFS that was also somewhat exciting at 4.2 months. And so, there is a potential clearly for targeting patients with HER2-high or HER2-positive with trastuzumab deruxtecan, and I think in the patients who are HER2-low, we need to better understand the potential utility. The common treatment-related adverse events that we see were the typical things that we've heard about with trastuzumab deruxtecan, but I think the one thing that was really worth noting was 8 patients or 25% of patients had interstitial lung disease (ILD), which we know is an important identified safety concern for patients who receive trastuzumab deruxtecan, and I think that's a pretty sizable number of 25%, so, I think that's going to really require a little bit more fleshing out for us to understand the safety for these patients. One question that a lot of us have had is whether these are patients who have received gemcitabine, which we know can also cause pneumonitis. And so, I don't know if we're seeing a higher percentage of ILD because of, 'priming' with prior gemcitabine. But regardless, I think this is just proof of principle that again, we need to identify patients with biliary tract cancers that have HER2-positivity because we now have a number of drugs including potentially trastuzamab deruxtecan to target [their disease] with after gemcitabine-based treatments Dr. Shaalan Beg: Absolutely. Any new biomarkers to keep on the radar for our listeners? Dr. Rachna Shroff: I think there are a lot of really exciting targets. One that was talked about and that we saw data on at ASCO [Annual Meeting] was from Abstract 4048, which looked at claudin [18]. Claudin is basically a transmembrane protein that kind of helps maintain the tight junctions between cells. In gastric cancer, in particular, we look at claudin 18 isoform 2, and there are 18.1 and 18.2 gene expressions that have been identified in gastric cancer. So, there was a very comprehensive abstract that was presented of over 1,900 samples that underwent comprehensive profiling by next-generation sequencing. And the patients were identified with claudin 18.1, and 18.2, high versus low. Claudin 18.2 expression was actually detected in 97% of the samples. It's slightly lower with claudin 18.1 at 63%. It's important to note that the primary tumors had higher expression levels than the metastatic tumors, so those were really the tumors in which they did a deeper dive. And in the process of doing this deeper dive, they did a really interesting kind of better understanding of the immune microenvironment and the immune profile in the samples that had claudin expression. And what was identified is that there was an inverse relationship basically between claudin 18.1 and 18.2 expression and correlation with PD-L1 positivity, tumor mutational burden (TMB)-high, M1 macrophages expression, NK cell presence, CD4 positive T-cells, myeloid dendritic cells. And so, there's clearly something between the presence of this claudin expression and the effect it has on the immune microenvironment. I think that's very relevant to keep in mind because as we all know, there's a whole space of drug development focused right now on anti-claudin 18.2 monoclonal antibodies, as well as a target for antibody-drug conjugates (ADC) and cellular therapies with CAR T-cell therapies being developed specifically against claudin 18. And so, understanding the immune microenvironment and the interaction between the claudin expression will be really important as we continue to charge forward in that space. Dr. Shaalan Beg: Absolutely. Very, very exciting. Sticking with the liver pancreas theme, what other studies piqued your interest with regards to hepatocellular carcinoma (HCC)? Dr. Rachna Shroff: It's a really exciting time in HCC. I mean, we actually have drugs that are working in the advanced space. And so, now there's a lot of interest in shifting to looking at preoperative neoadjuvant, and adjuvant approaches and what we can do to improve disease-free survival and overall survival in patients who are able to undergo prior resection. So, Abstract 4013 looked specifically at the efficacy and safety of adjuvant hepatic arterial infusion chemotherapy with FOLFOX. And this was a randomized open-label phase 3 trial. It actually included a total of 315 patients between 5 different centers and patients were randomly assigned to receive either 1 to 2 cycles of adjuvant HAIC FOLFOX (Hepatic Arterial Infusion Chemotherapy FOLFOX) versus just follow up, the control group had no adjuvant treatment, and the primary endpoint was disease-free survival here and in the intention to treat population, there was a significantly improved median disease-free survival at 27 months versus 11 months in the patients who were on the control arm. And there was a protocol analysis, there were a number of other efficacy endpoints including disease-free survival rates at 1, 2, and 3 years. And everything kind of leaned towards and or suggested an improvement with the utility of HAI FOLFOX in patients who undergo complete resection. It should be noted that this included patients specifically who had microvascular invasion on their resection. And so, these are patients who are at higher risk for recurrence as we know. This to me suggests that there could be a role for adjuvant treatment in patients who undergo complete resection with microvascular invasion (MVI). HAI is a very specific technique and it requires a highly skilled center in the placement of HAI pumps. And we're seeing more and more trials across the U.S. as well investigating the role of HAI in advanced disease and in perioperative approaches. And so, I think this is an area of much-needed continued research. There are, of course, a number of ongoing adjuvant studies looking at immunotherapy in the adjuvant setting. And so, it'll be really important to see how those read out and then to try to put all of these in context so that we can better understand local therapy like HAI FOLFOX versus more systemic adjuvant approaches like immunotherapy. Dr. Shaalan Beg: Thank you very much, Dr. Shroff for sharing your valuable insights with us. I really appreciate you taking the time to spend with us and our listeners. Dr. Rachna Shroff: Thanks so much. I enjoyed it. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, we'd really like to hear your feedback. If you could please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much! Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

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062: Nick Pifani - Pancreatic Cancer Survivor - Delran, New Jersey, USA

united states cancer cancer survivors chemotherapy pancreatic cancer whipple stage three new jersey usa folfirinox

Play Episode Listen Later Apr 4, 2022 35:45

Nick Pifani needed three different treatment regimens, but survived Stage Three pancreatic cancer. It took chemotherapy, then radiation treatment, then a Whipple surgical procedure, but he is in remission and has resumed his active pre-diagnosis life of running, swimming and cycling.

052: Teona Ducre, Pancreatic Cancer Survivor - Atlanta, Georgia USA

Play Episode Listen Later Mar 24, 2022 53:40

Teona Ducre survived first a misdiagnosis, then a correct diagnosis of Stage III pancreatic cancer. Even while going through treatment, which included chemotherapy, she was a vigorous advocate for those going through a pancreatic cancer journey. In remission since 2016, Teona is a blogger, a public speaker in the fight against cancer, and she is a tireless volunteer for the Pancreatic Cancer Action Network (PanCAN.org).

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New Directions With PARP Inhibitors in Pancreatic Cancer

CCO Oncology Podcast

Play Episode Listen Later Feb 21, 2022 18:47

In this episode, Eileen M. O'Reilly, MD, and Naureen Starling, MD, FRCP, discuss emerging therapeutic strategies involving PARP inhibitor therapy in the treatment of pancreatic cancer. Topics include:Current treatment landscape and testing in the United States vs the United Kingdom Testing for molecular subgroups beyond BRCAmUsing PARP inhibitors in earlier stages of the diseaseLearning from other cancers, such as prostate, breast, and ovarian Presenters:Eileen M. O'Reilly, MDWinthrop Rockefeller Chair in Medical OncologySection Head, Hepatopancreaticobiliary/Neuroendocrine CancersGastrointestinal Oncology ServiceAssociate DirectorDavid M. Rubenstein Center for Pancreatic CancerAttending Physician, MemberMemorial Sloan Kettering Cancer CenterProfessor of MedicineWeill Medical CollegeNew York, New York, USANaureen Starling, MD, FRCPAssociate Director of Clinical ResearchDepartment of GI CancersConsultant Medical Oncologist, GI CancersThe Royal Marsden HospitalLondon, United KingdomContent based on an online CME program supported by an educational grant from AstraZeneca.Link to full program:https://bit.ly/3s6AnSz

Exploratory Study of Metformin and Rapamycin as Maintenance Therapy

Oncotarget

Play Episode Listen Later Dec 1, 2021 6:20

Volume 11, Number 21 of Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival. Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, "Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting." Metformin is an antidiabetic drug in the biguanide class of agents which inhibits mTOR complex 1 primarily through AMP-kinase activation. A synergistic effect of the combination of metformin with rapamycin was suggested by preclinical studies demonstrating enhanced inhibition of mTOR in a pancreatic cancer cell line and better growth inhibition of pancreatic cancer cells in a xenograft tumor model with the combination than either agent alone. Based on this, they conducted an exploratory study of metformin with or without rapamycin in patients with mPDA in the maintenance setting. The Le Research Team concluded in their Oncotarget Research Article, "the administration of metformin with or without rapamycin in patients with mPDA who achieve a response to chemotherapy is well-tolerated and was associated with better than expected overall survival in this study. Additional studies are needed to prospectively evaluate the role of these agents compared to a maintenance chemotherapy or observation only approach." Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27586 DOI - https://doi.org/10.18632/oncotarget.27586 Full text - https://www.oncotarget.com/article/27586/text/ Correspondence to - Dung T. Le - dle@jhmi.edu Keywords - pancreatic cancer, mTOR inhibition, maintenance therapy, metformin About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957 Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC

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040: Nick Pifani - Pancreatic Cancer Survivor - Delran, New Jersey USA

united states cancer survivors chemotherapy pancreatic cancer whipple cancer cure stage three new jersey usa folfirinox

Play Episode Listen Later Sep 26, 2021 35:23

#85 – PRODIGE 23 – FOLFIRINOX associado a RT neoadjuvante para pacientes com câncer de reto localmente avançado

Clinical Papers Podcast

Play Episode Listen Later Jul 31, 2021 33:31

Publicado agora em abril de 2021, o PRODIGE 23 traz em seu resumo a conclusão de que, esse esquema de quimioterapia neoadjuvante deve mudar a prática clínica. Mas, como diz o Mário Sérgio Cortella: Será?!?!Ouça esse episódio 85 do Clinical Papers Podcast e descubra que a adição de irinotecano ao TNT com FOLFOX pode ser “demais” para melhorar os resultados relacionados ao tratamento de câncer de reto localmente avançado.Com uma revisão !TOP! sobre o tratamento de câncer de reto, os drs. Ranyell Spencer, Tiago Biachi e Allan Pereira mostram o que está nas entrelinhas desse importante estudo.Sejam bem-vindos ao episódio 85 do Clinical Papers PodcastPara saber mais sobre o paper, acesse: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00079-6/fulltext

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Clinical Challenges in Surgery HPB: Pancreatic Head Cancer

Behind The Knife: The Surgery Podcast

Play Episode Listen Later Jun 21, 2021 50:31

Description: Pancreatic adenocarcinoma is a highly lethal cancer with a dismal long-term prognosis requiring complex multidisciplinary planning in order to optimize outcomes. In this episode from the Hepato-Pancreato-Biliary team at Behind the Knife, we discuss a patient presenting with a borderline resectable pancreatic head mass. Learning Objectives: In this episode, we review risk factors for pancreatic adenocarcinoma, key steps of the diagnostic work-up and pre-operative planning, and definitions of resectable, borderline resectable, and unresectable tumors. The history of chemotherapy for pancreatic cancer is briefly reviewed, highlighting the importance of multi-agent regimens and role of neoadjuvant therapy. Finally, we highlight the critical steps of the Whipple procedure.Hosts:Timothy Vreeland, MD, FACS (@vreelant) is an Assistant 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-4 General Surgery resident at Brooke Army Medical Center Lexy (Alexandra) Adams, MD, MPH (@lexyadams16) is a PGY-3 General Surgery resident at Brooke Army Medical CenterLinks to Papers Referenced in this Episode Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survivalJ Gastrointest Surg. 2014 Jan;18(1):16-24 https://pubmed.ncbi.nlm.nih.gov/24241967/ Preoperative biliary drainage for cancer of the head of the pancreasN Engl J Med. 2010 Jan 14;362(2):129-37https://pubmed.ncbi.nlm.nih.gov/20071702/ 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experienceJ Gastrointest Surg. 2006 Nov;10(9):1199-210; discussion 1210-1.https://pubmed.ncbi.nlm.nih.gov/17114007/ Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trialJAMA. 2013 Oct 9;310(14):1473-81. https://pubmed.ncbi.nlm.nih.gov/24104372/ Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trialLancet. 2017 Mar 11;389(10073):1011-1024https://pubmed.ncbi.nlm.nih.gov/28129987/ FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic CancerN Engl J Med. 2018 Dec 20;379:2395-2406 https://www.nejm.org/doi/full/10.1056/NEJMoa1809775 Surgical Outcome Results From SWOG S1505: A Randomized Clinical Trial of mFOLFIRINOX Versus Gemcitabine/Nab-paclitaxel for Perioperative Treatment of Resectable Pancreatic Ductal AdenocarcinomaAnn Surg. 2020 Sep 1;272(3):481-486.doi: 10.1097/SLA.0000000000004155https://pubmed.ncbi.nlm.nih.gov/32740235/ ASCO Guidelines Potentially Curable Pancreatic Adenocarcinomahttps://www.asco.org/research-guidelines/quality-guidelines/guidelines/gastrointestinal-cancer#/12146 NCCN Guidelines Pancreatic Adenocarcinomahttps://www.nccn.org/guidelines/nccn-guidelines/guidelines-detail?category=1&id=1455

Expert Answers to HCP Questions on Pancreatic Cancer Treatment

CCO Oncology Podcast

Play Episode Listen Later Mar 22, 2021 13:13

In this episode, Michael J. Pishvaian, MD, PhD, and Rachna Shroff, MD, answer audience questions from a live CCO webinar focused on current best practices and emerging strategies in pancreatic cancer treatment, with questions including:What is your preferred regimen for neoadjuvant therapy in patients with resectable disease?How do you sequence therapy for patients with metastatic pancreatic cancer?How can you manage a patient who develops significant diarrhea with FOLFIRINOX?Are cisplatin and oxaliplatin equally efficacious for patients with BRCA-mutant disease?How should maintenance olaparib be used?Presenters:Michael J. Pishvaian, MD, PhD Associate Professor of OncologyDirector, Gastrointestinal, Developmental Therapeutics, and Clinical Research ProgramsNCR Kimmel Cancer Center at Sibley Memorial HospitalJohn Hopkins University School of MedicineWashington, DCRachna Shroff, MDAssociate Professor of MedicineChief, Section of GI Medical OncologyDirector, UACC Clinical Trials OfficeThe University of Arizona Cancer CenterTucson, Arizona Content based on an online CME program supported by educational grants from Bristol-Myers Squibb and Ipsen Group.Link to full program:http://bit.ly/314BALT

phd md polo cco cancer treatment chemotherapy michael j cme pancreatic cancer gastrointestinal brca bristol myers squibb targeted therapy mpact olaparib gemcitabine folfirinox

Multitumor | Oncology Today with Dr Neil Love: The Role of PARP Inhibition in the Management of Common Cancers

Oncology Today with Dr Neil Love

Play Episode Listen Later Dec 18, 2020 172:55

Featuring interviews with Drs Maha Hussain, Ursula Matulonis, Phillip A Phillip and Hope S Rugo on the following topics: PARP inhibitors for breast cancer — Hope S Rugo, MD (0:00) Case: A woman in her early 60s with dermatomyositis is diagnosed with ER-positive breast cancer and ovarian cancer and a germline BRCA1 mutation (36:48) DNA repair gene alterations and response to PARP inhibitors in breast cancer (40:26) PARP inhibitors in patients with advanced ovarian cancer (OC) — Ursula Matulonis, MD (46:46) Case: A woman in her mid-60s with advanced OC and a germline BRCA1 mutation achieves an excellent response to maintenance olaparib (1:06:04) Case: A woman in her early 60s with homologous recombination deficient advanced OC receives niraparib (1:07:54) Perspective on the use of neoadjuvant therapy for patients with OC; risks and benefits with PARP inhibitors for advanced OC (1:09:47) DNA repair and PARP inhibitors in pancreatic cancer — Philip A Philip, MD, PhD, FRCP (1:26:59) Case: A man in his mid-70s with locally advanced pancreatic cancer and a somatic BRCA1 mutation receives modified FOLFIRINOX followed by maintenance olaparib (1:51:12) Case: A man in his early 50s is diagnosed with metastatic pancreatic cancer, elevated bilirubin and mutations in BRCA1, APC, KRAS and p53 (2:00:10) Optimizing the use of PARP inhibition for prostate cancer (PC) — Maha Hussain, MD, FACP, FASCO (2:07:56) Case: A man in his late 60s with metastatic castration-resistant PC (mCRPC) and a germline BRCA2 mutation receives olaparib on the BRCAAway trial (2:30:35) Case: A man in his early 70s with mCRPC and a BRCA2 mutation achieves an excellent response to veliparib with abiraterone/prednisone on a clinical trial (2:33:46) Role of liquid biopsy in identifying mCRPC with BRCA1/2 mutations; ongoing trials investigating PARP inhibitors in PC (2:36:41) CME information and select publications

phd management er dna cancer md pc perspective optimizing oc oncology cme apc brca1 kras parp brca2 frcp neil love folfirinox parp inhibition

Dr Michael Pishvaian Comments on the Use of PARP Inhibition in the Management of Pancreatic Cancer

Play Episode Listen Later Jun 17, 2020 15:13

Is it worthwhile to treat pancreatic cancer? Dr Michael Pishvaian from Johns Hopkins University discusses the use of the PARP inhibitor olaparib and other new developments in the disease. Additional Resources * Golan T et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 2019;381:317-27. Full text (https://www.nejm.org/doi/full/10.1056/NEJMoa1903387?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed) * Burris HA 3rd et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreatic cancer: A randomized trial. J Clin Oncol 1997;15(6):2403-13. Abstract (https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.6.2403) * Conroy T et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25. Correspondence (https://www.nejm.org/doi/full/10.1056/NEJMc1107627?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed) * Von Hoff DD et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703. Full text (https://www.nejm.org/doi/10.1056/NEJMoa1304369?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov) * Doleh Y et al. Treatment patterns and outcomes in pancreatic cancer: Retrospective claims analysis. Cancer Med 2020;9:3463-76. Full text (https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.3011) * Mavros MN et al. Low rates of specialized cancer consultation and cancer-directed therapy for noncurable pancreatic adenocarcinoma: A population-based analysis. CMAJ 2019;191(21):E574-80. Full text (https://www.cmaj.ca/content/191/21/E574.long) * Lowery MA et al. Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms. JNCI 2018;110(10):1067-74. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186514/) * O’Reilly EM et al. Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation. J Clin Oncol 2020;38(13):1378-88. Full text (https://ascopubs.org/doi/full/10.1200/JCO.19.02931?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)

An exploratory study of metformin and rapamycin as maintenance therapy

Oncotarget

Play Episode Listen Later May 28, 2020 2:03

PRESS RELEASE https://www.eurekalert.org/pub_releases/2020-05/ijl-aes052720.php# Volume 11, Number 21 of @Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival. Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, "Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting." Metformin is an antidiabetic drug in the biguanide class of agents which inhibits mTOR complex 1 primarily through AMP-kinase activation. A synergistic effect of the combination of metformin with rapamycin was suggested by preclinical studies demonstrating enhanced inhibition of mTOR in a pancreatic cancer cell line and better growth inhibition of pancreatic cancer cells in a xenograft tumor model with the combination than either agent alone. Based on this, they conducted an exploratory study of metformin with or without rapamycin in patients with mPDA in the maintenance setting. The Le Research Team concluded in their Oncotarget Research Article, "the administration of metformin with or without rapamycin in patients with mPDA who achieve a response to chemotherapy is well-tolerated and was associated with better than expected overall survival in this study. Additional studies are needed to prospectively evaluate the role of these agents compared to a maintenance chemotherapy or observation only approach." ### Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/oncotarget.27539 Full text - https://www.oncotarget.com/article/27586/text/ Correspondence to - Dung T. Le - dle@jhmi.edu Keywords - pancreatic cancer, mTOR inhibition, maintenance therapy, metformin About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105

study md llc baltimore soundcloud reddit pinterest johns hopkins pda press releases correspondence metformin pancreatic mtor exploratory rapamycin maintenance therapy folfirinox altmetric oncotarget

Pancreatic Cancer | Michael J Pishvaian, MD, PhD

Play Episode Listen Later Jan 24, 2020 65:05

Pancreatic Cancer Update, Issue 1, 2020 — Our interview with Dr Pishvaian highlights the following topics as well as cases from his practice: Key biologic features of pancreatic cancer (0:00) Genetic alterations and potentially actionable mutations in pancreatic cancer (2:02) Targeting BRCA mutations in pancreatic cancer; incidence of microsatellite instability-high disease (4:44) Current recommendations for genetic testing for patients with pancreatic cancer (6:45) Molecular profiling for patients with pancreatic cancer: The Know Your Tumor® initiative (11:36) Ongoing trials investigating targeted therapies for pancreatic cancer (12:56) Case: A woman in her early 60s with metastatic pancreatic cancer (mPC) and a germline BRCA2 mutation is enrolled on a clinical trial of veliparib with FOLFOX as first-line therapy(14:46) Activity, safety and ongoing evaluation of PARP inhibitors in combination with chemotherapy for mPC (18:05) Case: A woman in her early 60s with mPC and a somatic BRCA2 mutation receives FOLFIRINOX followed by maintenance rucaparib on a clinical trial (20:29) POLO: Design and results of a Phase III trial of olaparib as maintenance therapy for patients with mPC and a germline BRCA mutation after first-line chemotherapy (23:38) Tolerability of maintenance olaparib on the POLO trial (27:42) Clinical implications of the POLO trial results (30:09) Case: A woman in her late 50s with locally advanced pancreatic cancer and a germline ATM mutation is enrolled on a clinical trial of irinotecan, a PARP inhibitor and an ATR inhibitor (34:31) Response to FOLFOX in patients with locally advanced pancreatic cancer and ATM mutations (37:37) Case: A man in his early 60s with mPC with a ROS1 fusion receives entrectinib on a clinical trial (41:22) Clinical experience and dosing considerations with FOLFIRINOX or gemcitabine/nab paclitaxel (44:03) Use of nal-IRI (nanoliposomal irinotecan) with 5-FU/leucovorin for mPC (46:58) Importance of supportive and palliative care for patients with mPC (48:19) Perspective on the use of medical marijuana for patients with mPC (51:47) Choice of gemcitabine/nab paclitaxel or FOLFIRINOX as first-line therapy for mPC (53:43) Selection of adjuvant therapy for patients with pancreatic cancer (55:53) Case: A woman in her mid-50s with localized pancreatic cancer receives neoadjuvant FOLFIRINOX (57:49) Potential role of PARP inhibitors for pancreatic cancer in the adjuvant setting (1:02:24) CME information and select publications

Pancreatic Cancer | Talia Golan, MD

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Jan 24, 2020 76:48

Pancreatic Cancer Update, Issue 1, 2020 — Our interview with Dr Golan highlights the following topics as well as cases from her practice: Case: A man in his mid-40s with borderline-resectable adenocarcinoma of the pancreas (PAD) receives neoadjuvant FOLFIRINOX (0:00) Indications for adjuvant therapy in patients with borderline-resectable PAD (3:25) Management of borderline-resectable PAD (5:36) Selection of neoadjuvant therapy for patients with pancreatic cancer (8:06) Incidence of BRCA mutations in Israel and the United States (11:51) Case: A woman in her late 70s with node-positive, resectable PAD and multiple comorbidities receives adjuvant gemcitabine/capecitabine (14:03) Dosing and tolerability of gemcitabine/capecitabine as adjuvant therapy for elderly patients (17:36) Perspective on the role of surgical resection for older patients with pancreatic cancer (20:59) Results of the Phase III APACT trial of adjuvant gemcitabine/nab paclitaxel versus gemcitabine alone for surgically resected PAD (23:25) Choice of FOLFIRINOX versus gemcitabine/nab paclitaxel as first-line therapy for mPC (26:35) Reduction in the risk of recurrence with adjuvant therapy (28:38) Perspective on palliative and supportive care for patients with mPC (34:25) Importance of maintaining quality of life and managing depression for patients with pancreatic cancer (40:02) Role of medical marijuana in managing symptoms and treatment side effects in pancreatic cancer (42:56) Single-shot celiac plexus radiosurgery in pancreatic cancer: Palliation and functional outcomes (46:15) Molecular profiling for patients with pancreatic cancer; spectrum of mutations in DNA damage repair genes (48:43) Design, eligibility and endpoints of the Phase III POLO trial evaluating olaparib as maintenance therapy after first-line platinum-based chemotherapy for patients with mPC and a germline BRCA mutation (52:43) POLO trial results and clinical experience with olaparib as maintenance therapy (57:02) Selection and sequencing of therapy for patients with BRCA mutations (59:53) Side effects associated with PARP inhibitors in patients with pancreatic cancer (1:04:51) Response to first-line FOLFIRINOX followed by maintenance olaparib (1:06:44) Novel approaches in the management of pancreatic cancer (1:11:40) CME information and select publications

Optimizing Treatment Strategies for Germline BRCA/PALB2 Mutant Pancreatic Adenocarcinoma

Play Episode Listen Later Jan 21, 2020 9:22

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.

Episode 3: The Chemo Commences

The Adventures of PanCan Man

Play Episode Listen Later Dec 9, 2019 52:31

Take a little tour with me today when I tell you all the details of my experience with my first chemotherapy round of FOLFIRINOX. That four-drug combination has proved to be a lifesaver for people like me who have pancreatic cancer. But I can tell you there are consequences for using such a powerful drug cocktail -- and I experienced them all. You'll learn about my neurotoxicity. About a cholinergic crisis. About the application of atropine. And how I thought I'd seen my last day on my first day of chemo.

cancer chemo pancreatic folfirinox

Gastrointestinal Cancer Research From ESMO 2019

The ASCO Post Podcast

Play Episode Listen Later Oct 31, 2019 22:04

This week, we discuss two studies in gastrointestinal cancers presented at this year's European Society for Medical Oncology Congress. First up, the NEOLAP trial assessed induction chemotherapy with nab-paclitaxel plus gemcitabine or sequential FOLFIRINOX followed by surgical exploration in patients with locally advanced pancreatic cancer. Next, we'll discuss the ClarIDHy study, which examined treatment with ivosidenib in patients with advanced cholangiocarcinoma and an IDH1 mutation. We'll hear from the lead authors of each of these studies, and we'll also hear a discussion about the use of cabozantinib in advanced hepatocellular carcinoma, with Dr. Tim Meyer and Dr. Lorenza Rimassa, co-investigators for the CELESTIAL trial.Coverage of stories discussed this week on ascopost.com:ESMO 2019: High Conversion Rate With Certain Induction Chemotherapy Regimens Is Associated With Improved Overall Survival in Locally Advanced Pancreatic CancerESMO 2019: Ivosidenib in IDH1-Mutated Advanced Cholangiocarcinoma

coverage celestial cancer research gastrointestinal european society esmo tim meyer idh1 folfirinox

Episódio 12 - Tratamento neoadjuvante com QT/RT e LOSARTANA para tumores de pâncreas

Clinical Papers Podcast

Play Episode Listen Later Jul 17, 2019 29:32

O que vocês acham de acrescentar LOSARTANA ao FOLFIRINOX para o tratamento do câncer de pâncreas? Será que faz sentido?!?! Neste episódio discutimos um estudo fase II que avaliou a adição dessa droga ao tratamento de QT/RT como estratégia de neoadjuvância para tumores localmente avançados. Publicado na JAMA Oncol. 2019;5(7):1020-1027, esse esquema inovador trouxe resultados surpreendentes! Ouça também nossa discussão e aprenda mais sobre critérios de ressecabilidade e o que é o tão famoso NCCN. Ouça este mais novo episódio do Clinical Papers Podcast! Para saber mais sobre o estudo publicado na revista JAMA Oncol., acesse o link: https://jamanetwork.com/journals/jamaoncology/article-abstract/2734827

neste epis tratamento publicado tumores nccn folfirinox

Gastrointestinal Cancers | Addressing Current Questions and Controversies in the Management of Gastrointestinal Cancers

Play Episode Listen Later Jul 11, 2019 151:30

Proceedings from a CME symposium held at the 2019 ASCO Annual Meeting. Featuring perspectives from Prof Dirk Arnold and Drs Tanios Bekaii-Saab, Joseph Chao, Anthony El-Khoueiry, Richard S Finn, Yelena Y Janjigian, Scott Kopetz and Eileen M O'Reilly. Introduction (00:00) Program overview: Dr Love Hepatocellular Carcinoma (HCC) — Dr El-Khoueiry and Dr Finn (2:01) Case (Dr Gujja): A man in his mid-70s with Child-Pugh A multifocal HCC and a tumor thrombus in the midhepatic vein extending into the floor of the right atrium (2:12) Case (Dr Park): A woman in her early 70s with Child-Pugh B HCC who developed hand-foot syndrome and required a dose reduction while receiving first-line sorafenib and now has progressive disease (16:11) Pancreatic Adenocarcinoma (PAD) — Dr Bekaii-Saab and Dr O'Reilly (41:01) Case (Dr Ibrahim): A man in his late 50s with symptomatic metastatic PAD who experienced a dramatic response to modified FOLFIRINOX (52:14) Cases (Dr Park and Dr Morganstein): Elderly patients with metastatic PAD, poor performance status and disease progression on nab paclitaxel/gemcitabine (1:00:22) Case (Dr Gujja): A woman in her late 60s with metastatic PAD and a germline BRCA2 mutation (1:06:00) Gastric/Gastroesophageal (GEJ) Cancers — Dr Chao and Dr Janjigian (1:20:30) Case (Dr Favaro): A man in his late 30s with HER2-positive metastatic gastric cancer who received paclitaxel/ramucirumab after disease progression and worsening neuropathy on FOLFOX/trastuzumab (1:35:52) Case (Dr Morganstein): A man in his mid-60s with microsatellite-stable, PD-L1-negative metastatic GEJ cancer who attained a complete response to second-line nivolumab (1:39:34) Colorectal Cancer (CRC) — Prof Arnold and Dr Kopetz (1:52:56) Case (Dr Morganstein): A woman in her early 40s with widespread RAS wild-type, microsatellite-stable, left-sided metastatic CRC (mCRC) (1:57:43) Case (Dr Ibrahim): A woman in her late 70s with MSI-high mCRC who refused chemotherapy and experienced a completed response to pembrolizumab (2:04:01) Case (Dr Favaro): A woman in her late 80s with RAS wild-type, microsatellite-stable, right-sided mCRC with a BRAF V600E tumor mutation who received BRAF-targeted therapy (2:13:49) Select publications

Oncology Grand Rounds Series: Part 1 — Gastrointestinal Cancers

ASCO Guidelines Podcast Series

Play Episode Listen Later Jun 24, 2019 89:42

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

video cancer series select rounds oncology tas pancreatic cancer crc gastrointestinal msi hcc iri grand rounds jessica mitchell folfirinox folfox folfiri eileen m o'reilly

Potentially Curable Pancreatic Adenocarcinoma Guideline Update

Play Episode Listen Later Jun 10, 2019 7:49

An interview with Dr. AloK Khorana from Cleveland Clinic on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." This guideline update adds another treatment regimen to the options for patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines See all of ASCO's podcasts at www.asco.org/podcasts The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Alok Khorana from The Cleveland Clinic, lead author on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." Thank you for being here today, Dr. Khorana. Thank you for having me. So this guideline was first published in 2016. And then we saw an update in 2017. And now we've just updated it again. So can you tell the listeners what has prompted these updates? In the world of pancreatic cancer, this has been an evolution in adjuvant treatment, which is sort of a surprise, because we've been treating pancreatic cancer in a very similar fashion over the past several decades. And between the 1990s and until just a few years ago, there hasn't really been much progress in terms of what to do with pancreatic cancer patients after they've had their cancer resected. It's pretty clear that these patients should not have just the surgery, that they should have additional treatment after the surgery. And for decades, the standard treatment after surgery was either 5-fluorouracil or gemcitabine, but most oncologists are opting for gemcitabine. The two recent updates of the ASCO Guidelines reflect two large randomized trials that have been published in this area. The first changed-- added a new standard of care, which was a doublet adjuvant therapy with gemcitabine and capecitabine. And the reason for this most recent update is the publication of a large randomized trial of adjuvant FOLFIRINOX for patients with pancreatic cancer that was published in December 2018 in "The New England." And we felt that the results were so compelling that we needed to update the guidelines so oncologists and practitioners would have the most current data to help them make decisions for patients. So for our listeners who may not now, can you tell us what changes have been made to the recommendations in this newest version of the guideline? So this is a guideline on a potentially curable pancreatic adenocarcinoma, which is we are saying these are resectable pancreatic cancer patients. And the guideline update changes primarily one recommendation, recommendation 4.1, which is a listing of additional adjuvant therapy options. As I mentioned earlier, the most common monotherapy option used to be the gemcitabine 5-fluorouracil. And that recently changed to doublet therapy. And we've kept those recommendations, but we've added the modified combination regimen of 5-fluorouracil, oxaliplatin, and irinotecan, which is known as the FOLFIRINOX regimen. And we are making this the preferred regimen for patients in the absence of concerns for toxicity or tolerance. We are still keeping the recommendations for the doublet therapy with gemcitabine capecitabine as well as monotherapy with gemcitabine alone or fluorouracil with cholanic acid. But those are not the preferred regimens, because the data for FOLFIRINOX is much better than prior regimens. Having said that, there are concerns about using such an aggressive regimen and in patients who have undergone a major surgery. So patients have not recovered from operation, then it's reasonable to consider one of the other regimens. But the update primarily focuses on adding adjuvant FOLFIRINOX as the preferred option in the adjuvant setting. And how has this guideline and its updates affected care for patients with pancreatic adenocarcinoma? I think since the results of this trial, the PRODIGY 24 trial came out of post-operative FOLFIRINOX. Almost every oncologist I know that focuses on treating patients with pancreatic cancer has suddenly added its use in patients that respected pancreatic cancer who are healthy enough to tolerate adjuvant FOLFIRINOX therapy. So it's definitely a practice-changing landmark paper. The results of the study were really quite impressive. The use of adjuvant therapy with FOLFIRINOX led to much longer survival than we've seen in any trial of adjuvant therapy of pancreatic cancer, almost 54 months-- or actually just over 54 months, almost 55 months-- in patients who are randomized to the modified FOLFIRINOX group and about 35 months in the gemcitabine alone group. The overall survival at three years was 63% in FOLFIRINOX and nearly 49% in the gemcitabine group. So that's a big difference at three-year survival as well. The one thing clinicians should be aware of is that this adjuvant therapy trial used a modified dose of FOLFIRINOX. They initially started off at the full those, which is 85 milligrams per meter squared of oxaliplatin, 400 mg per meter squared of leucovorin, and 180 milligrams per meter square of irinotecan. But the dose of iriniotecan was reduced part way through the study to 150 milligrams per meter squared, along with, of course, the conventional 2.4 grams or 5-fluorouracil over 46 hours. This modification of the irinotecan dose from 180 down to 150 is what many patients on the study received and was the more tolerable regimen and allowed the study to be completed. So the Guidelines Panel felt quite strongly that when using FOLFIRINOX in the adjuvant setting, we should stick with this modified dose, which is a lower dose of irinotecan at 150 milligrams per meter squared. And I think it's important that clinicians be aware of this distinction. And so taking this into account, many of us have made this recommendation to patients who are healthy enough to tolerate adjuvant FOLFIRINOX. And the hope is that this guideline will inform this ongoing practice as it changes in response to new data. And finally, what trials or new research are you keeping an eye on that may prompt an update for this guideline in the future? The results of another large adjuvant therapy trial are expected, hopefully at ASCO this year. This trial is the APAC trial that utilizes gemcitabine and nab-paclitaxel or Abraxane. This doublet combination is quite widely used in patients with metastatic pancreas cancer, particularly those patients for whom we feel FOLFIRINOX may not be appropriate because of their performance status or functional status. And the hope was that the doublet combination would also have good success in the adjuvant therapy setting and perhaps be a better option than the gem-cape doublet. There has been a press release from the sponsor of that trial, and it looks like the trial was not successful, although the way the press release is worded is rather confusing. So we wait for the full results of that trial to be presented at ASCO before we have an understanding of whether that is an appropriate regimen to use or not in the adjuvant setting. So that's certainly one large trial that many of us have been looking forward to complete sort of the set of ongoing adjuvant therapy trials in this setting. Great. It sounds like there's some really exciting things happening in pancreatic cancer right now. And I look forward to seeing this guideline evolve with the research. So Dr. Khorana, thank you so much for coming on the podcast today and summarizing the Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. Thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

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Episódio 1 - “FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer”

Clinical Papers Podcast

Play Episode Listen Later Apr 30, 2019 27:17

Neste primeiro episódio, discutimos um paper publicado na revista “The New England Journal of Medicine” intitulado: “FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer” cujo principal autor é o pesquisador T. Conroy do grupo PRODIGE ou Canadian Cancer Trials Group and the Unicancer Group. O gap do estudo é saber se a utilização de FOLFIRINOX como terapia adjuvante aumenta sobrevida em pacientes operados por adenocarcinoma de pâncreas. Foram randomizados 493 pacientes, após a ressecção do tumor entre fazer folfirinox ou gencitabina como esquemas de quimioterapia adjuvantes. Com uma mediana de follow up de 33,6 meses o grupo que fez folfirinox teve melhores resultados de sobrevida (21,6 vs. 12,8 meses) quando comparado com gencitabina. O que gerou um hazard ratio de 0,58. Quer saber mais sobre o paper N Engl J Med 2018;379:2395-406, acesse: https://www.ncbi.nlm.nih.gov/pubmed/30575490

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Pancreatic | Interview with E Gabriela Chiorean, MD

Play Episode Listen Later Mar 14, 2019 65:24

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

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Pancreatic | Interview with Andrew H Ko, MD

Play Episode Listen Later Mar 14, 2019 77:29

Pancreatic Cancer Update – Part 1: Our interview with Dr. Ko highlights the following topics as well as cases from his practice: Case: A 45-year-old woman with borderline resectable adenocarcinoma of the pancreas attains an excellent response to neoadjuvant FOLFIRINOX: 0m0s Role of genetic counseling and molecular profiling for patients with pancreatic cancer: 1m42s Effects of mutational load and PD-L1 expression on response to immunotherapy: 4m34s Pathophysiology of pancreatic cancer: 5m43s Radiographic criteria for defining resectable versus borderline resectable disease and implications for therapy: 8m3s Response and tolerability with neoadjuvant FOLFIRINOX: 12m14s Ongoing Phase II SWOG-S1505 trial of perioperative modified FOLFIRINOX (mFOLFIRINOX) versus gemcitabine/nab paclitaxel for resectable adenocarcinoma of the pancreas: 17m22s Efficacy of neoadjuvant chemotherapy for patients with resectable pancreatic cancer: 20m6s Case: A 78-year-old man with resected pancreatic cancer treated with adjuvant single-agent gemcitabine: 24m56s Risk of recurrence for patients with resectable pancreatic cancer: 28m31s Results from the Phase III PRODIGE 24/CCTG PA.6 trial evaluating adjuvant mFOLFIRINOX versus gemcitabine for patients with resected pancreatic ductal adenocarcinoma: 32m25s Risks and benefits with nab paclitaxel/gemcitabine and FOLFIRINOX as adjuvant therapy: 33m49s Case: A 70-year-old man with metastatic adenocarcinoma of the pancreas develops severe peripheral neuropathy with gemcitabine/nab paclitaxel as first-line therapy: 37m13s Peripheral neuropathy associated with nab paclitaxel: 39m40s Approach to first-line therapy for metastatic pancreatic cancer: 41m40s Combination immunotherapeutic approaches under investigation for advanced pancreatic cancer: 45m25s Efficacy and tolerability of the pegylated recombinant human hyaluronidase enzyme PEGPH20 in patients with advanced pancreatic cancer: 47m14s Therapeutic options for patients with metastatic pancreatic cancer and disease progression on gemcitabine/nab paclitaxel: 51m25s NAPOLI-1: Results of a Phase III trial of nanoliposomal irinotecan (nal-IRI) and 5-FU/leucovorin (LV) for metastatic pancreatic cancer after gemcitabine-based therapy: 57m15s Palliative care for patients with metastatic pancreatic cancer: 1h0m15s Case: A 54-year-old woman with locally advanced pancreatic cancer and refractory ascites: 1h4m45s Case: 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: 1h8m44s Case: A 62-year-old woman with pancreatic cancer and a solitary liver lesion receives FOLFIRINOX followed by stereotactic body radiation therapy: 1h12m55s Select publications

Key Takeaways from the 2019 Gastrointestinal Cancers Symposium with Dr. Stephen Leong