Podcasts about Gemcitabine

JCO Editorial Fellow Peter Li and JCO Associate Editor Eileen O'Reilly discuss the ASCO 25 Simultaneous Publication paper "Tumor-Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Peter Li: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Peter Li, and I'm joined by JCO Associate Editor Dr. Eileen O'Reilly to discuss the Journal of Clinical Oncology article and abstract presentation "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Now, let's start with the relevance of the article. Eileen, can you explain this study to our listeners? Dr. Eileen O'Reilly: Thanks very much, Peter, for the invitation today to discuss this. Yes, so this is a positive phase 3 trial that was conducted in locally advanced, unresectable pancreas cancer. Patients were randomized to receive either gemcitabine and nab-paclitaxel, international standard, with or without tumor-treating fields. And this is a device like a battery pack that you would wear with a goal to wear that approximately 18 hours a day. And the primary endpoint of this study was overall survival, with key secondary endpoints of tumor response, progression-free survival, looking at pain-free survival, and distant progression-free survival. So, the primary endpoint was met with a median overall survival of 16.2 months compared to 14.2 months on the intervention versus control arm, with a hazard ratio of 0.82. And so that met the pre-specified boundary. There was not an increase in progression-free survival, but there was an increase in control of pain on the tumor-treating fields study. So, it was a large, global study, community, academic sites, randomized 570 people, and it supports what I think we've seen in other difficult-to-treat malignancies using tumor-treating fields, that there's a signal of interest. Dr. Peter Li: Can you speak to some of the strengths and weaknesses of this study? Dr. Eileen O'Reilly: So, strengths: it was a large study. It included community sites, it included academic sites. It included ECOG performance status 0, 1, and some patients with 2. The intent was locally advanced. It probably is fair to say that there were some patients who had more advanced disease based on early progression, based on relatively high CA 19-9 for a percentage of people. But likely that was, with random assignment, that would have presumably fallen out between the arms. The inclusion of patients with a lower performance status is nice to see in large phase 3 studies in pancreas cancer. So, they would be some of the strengths. So maybe some of the limitations are the fact that it's an open-label study - so, always some biases inherent in that. Acknowledging that the primary endpoint was overall survival, presumably that wouldn't be directly influenced by that. And there was an imbalance of women on the control arm, and women do fare a little better in this disease, so possibly kind of weighted one of the study arms a little bit. But nonetheless, I think it was a rigorously designed and rigorously conducted phase 3 trial. It's always hard to fully interpret the signal in locally advanced disease because of the fact that some patients go on to surgery, some patients have a treatment switch of cytotoxic therapy, some patients will go on to radiation. And the endpoint here of overall survival, to a degree, eliminates some of that. So, the benchmark, I think, was generally high here. Dr. Peter Li: Gotcha. And then with these findings and this positive study, how do you foresee this research being implemented and how it will impact clinical practice moving forward? Dr. Eileen O'Reilly: I think there'll be an educational need to introduce this approach to the community and to the pancreas cancer world. Again, there's a precedent in glioblastoma and data from other diseases, so there's some familiarity with this. I think people always want to understand how it works and why it works, and that's something that we'll look forward to hearing more about mechanistically, and also seeing how it can be built upon. And there's some intriguing data with the combination of tumor-treating fields and immunotherapy that's being evaluated in the PANOVA-4 study. So, we'll stay tuned to hear how that reads out in due course. But I think overall, it'll be educational and learning, managing the cutaneous impacts or some skin irritation effects from this, and building on this signal in locally advanced disease. Dr. Peter Li: Well, thank you so much, Eileen, for your time and for speaking about the JCO article, "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

What John Morley originally thought was a urinary tract infection turned out to be a diagnosis of bladder cancer.  At first, he was told it was a mild form of the disease.  Then the diagnosis was upgraded to T2 Muscle Invasive Bladder Cancer, requiring a radical cystectomy meaning he would need to get his bladder removed.  His care team next told John he would also have to get his prostate taken out.  Next a mass was detected on his spleen, which meant that it, too, would have to be removed.  Treatment and recovery were tough, but he now urinates into a bag known as an ileal conduit, has become acclimated to it and leads a healthy lifestyle.   John Morley of Haymarket, Virginia is a Navy veteran who enjoyed scuba diving, hiking and other outdoor activities when in late 2021, he noticed blood in his urine.  He sought medical attention with his primary care physician, who upon learning of John's symptoms, referred him to a urologist.  The urologist called for cystoscopy, a procedure in which a camera is inserted in the patient's urethra, and based on its results, said a biopsy would be needed.   John received a blend of bad and good news.  He was told he had bladder cancer, but because it was T1 Non-Muscle Invasive Bladder Cancer, the cancer had not spread from his bladder.  John and his wife felt like celebrating and went out to dinner.   However, a short time later, John Morley was called back into the doctor's office.  He and his wife were told a followup check of his pathology report showed his cancer had been upgraded to T2 Muscle Invasive Bladder Cancer.  Not only did this mean John would have to undergo a radical cystectomy to remove his bladder, but the procedure would have to be preceded by two or three months of chemotherapy, a regimen that would include cisplatin and gemacitabine.   As he wondered what life would be like without a bladder, the news for John got worse.  He was told he would have to undergo a prostatectomy for the removal of his prostate.  Then a mass was detected in his spleen, and the spleen would have come out as well, all three in the same surgery.   The multi-faceted surgery was a success, but John had to decide how he was going to urinate.  Over two other options, he chose an ileal conduit.  It was attached to his stomach, close to his navel.  The urine drained into a urostomy bag.   Following the operation, John relied on walking to help him slowly regain his strength.  He has a good command of his use of the urostomy bag, and though it wasn't what he enjoyed pre-diagnosis, John Morley has returned to a healthy lifestyle that includes scuba diving.   Additional Resources:   Support Group: The Bladder Cancer Advocacy Group: https://www.bcan.org   John Website: https://www.beatbladdercancer.org            

Drs Park and Sonpavde discuss the CheckMate901 trial, which showed survival improvements with nivolumab plus chemotherapy in metastatic urothelial cancer.

An ultrasound revealed a large mass in Melinda Bachini's liver, and that led to a diagnosis of cholangiocarcinoma, a form of bile duct cancer.  Doctors removed two thirds of her liver.  Unfortunately, her cancer returned three months.  Melinda was hoping to take part in a clinical trial, but when insurance wouldn't cover a clinical trial, settled for a chemotherapy regimen.  When the chemo didn't help but left her with a bunch of awful side effects, she decided to end the chemotherapy treatment and live as long as she could.  Then she and her husband found out about another opportunity for a clinical trial, pursued it, qualified for it.  The trial led to her achieving survivorship.

When Kay Kays was diagnosed with pancreatic cancer in 1994, she not only had few treatment options, but she had no way of knowing this would be the first of four such diagnoses; but she survived each one, the last in 2008, and is still going strong.  She is now able to do just about everything she could do prior to her initial diagnosis and continues the fight as a cancer research advocate.

April 12, 2024Mark and Scott discuss questions that have come into the PRS communities:Hi is there any documentation, regarding the age limit for G2211 or 99459?Our MD think that they only apply to patients over 65 years old.  Is this true or is there documentation stating we can use them on patients under 65 years old.  If a patient fails a Trial of void, and a catheter is placed, would the 51700 be coded or just 51702? Should it matter if pass its fail? The service was still performed. And the 51702 is a component of the 51700.What are the codes that I use for gemcitibine bladder installation in the office. I know I would use 51720 would be the cpt code but how do i bill for the medicine?For Scrotoplasty, complicated (CPT 55180), Does it need to be performed with either Graft of Flap, to call for "complicated"? I am trying to differentiate between 55175 (scrotoplasty, simple) and 55180 (scrotoplasty, complicated), thank you! New Courses Available for Urologists and Urology APPsDocumentation for Reimbursement Challenge for Urologists​ Use Special Discount Code:DRC5624 and Save 36% ​Documentation for Coding and Reimbursement for APPs​ Use Special Discount Code: DCRA5624 and Save 36%Certification for Urology CodersDocumentation, Coding, and Billing Certification Course for Urology CodersUse Special Discount Code: DCBSC5624 and Save 36%PRS Billing and Other ServicesClick Here to Get More Information and Request a Quote   The Thriving Urology Practice Facebook group.The Thriving Urology Practice Facebook Group link to join:https://www.facebook.com/groups/ThrivingPractice/    Join the discussion:Urology Coding and Reimbursement Group - Join for free and ask your questions, and share your wisdom.Click Here to Start Your Free Trial of AUACodingToday.com

Dive into Dean Karrel's powerful journey as a bladder cancer survivor, from his initial diagnosis to life after a radical cystectomy, in Episode 66 of Bladder Cancer Matters. Dean shares the symptoms that led to his life-changing diagnosis, the resilience he maintained through treatments that failed him like BCG and Gemcitabine, and his decision for life-saving surgery. His story is a unfiltered look at the challenges post-surgery, the crucial role of support from nurses and care teams, and his gratitude towards them. Dean highlights the importance of organizations like BCAN in supporting bladder cancer patients and calls on patients to advocate for themselves, ask questions, and live fully post-diagnosis. His journey isn't just about survival; it's an inspiring call to action, emphasizing strength, advocacy, and hope. Join us to be moved and motivated by Dean's indomitable spirit. Don't forget to subscribe to Bladder Cancer Matters and comment and share this podcast with family and friends.

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.

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.

Drs Sumanta Pal and Pavlos Msaouel discuss the unique pathophysiology of renal medullary carcinoma, treatment options, clinical trials, and the importance of screening and early detection. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984239). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Renal Medullary Carcinoma and Its Association With Sickle Cell Trait: A Case Report and Literature Review https://pubmed.ncbi.nlm.nih.gov/32218668/ Renal Medullary Carcinoma: The Kidney Cancer That Affects Individuals With Sickle Cell Trait and Disease https://pubmed.ncbi.nlm.nih.gov/28697316/ Renal Medullary Carcinoma: A National Analysis of 159 Patients https://pubmed.ncbi.nlm.nih.gov/28485059/ Sickle Cell Trait https://pubmed.ncbi.nlm.nih.gov/30725815/ 2004 WHO Classification of the Renal Tumors of the Adults https://pubmed.ncbi.nlm.nih.gov/16442207/ Renal Cell Carcinoma Unclassified With Medullary Phenotype in a Patient With Neurofibromatosis Type 2 - PubMed (nih.gov) https://pubmed.ncbi.nlm.nih.gov/36975468/ Association of High-Intensity Exercise With Renal Medullary Carcinoma in Individuals With Sickle Cell Trait: Clinical Observations and Experimental Animal Studies https://pubmed.ncbi.nlm.nih.gov/34885132/ Metastatic Renal Medullary and Collecting Duct Carcinoma in the Era of Antiangiogenic and Immune Checkpoint Inhibitors: A Multicentric Retrospective Study https://pubmed.ncbi.nlm.nih.gov/35406448/ Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer https://clinicaltrials.gov/ct2/show/NCT03587662 Phase II Trial of Immunotherapy in Patients With Carcinomas Arising From the Renal Medulla https://clinicaltrials.gov/ct2/show/NCT05347212

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.  

When Anne Shimabukuro, a healthy mother of two, noticed a sharp pain in her left side in 2005, one that manifested itself when she ate, she immediately sought medical attention.  That led to a diagnosis of a malignant tumor in her pancreas.  She wasted no time in getting part of her pancreas removed.  It required a surgical procedure, followed by chemotherapy and radiation therapy.  Anne survived pancreatic cancer and today enjoys a healthy lifestyle.

Gemcitabine is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by intravenous infusion. In today's episode, we have discussed broader aspects of Gemcitabine that may be useful to cancer patients and their caregivers. Hope this helps. See you soon. Jai Hind

Drs Sumanta Pal and Mehmet Asim Bilen discuss the complexities of treating patients with non–clear cell renal carcinoma, the nuances of rare subtypes, and when to use chemotherapy vs immunotherapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968741). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Renal Cell Carcinoma https://emedicine.medscape.com/article/281340-overview Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology https://pubmed.ncbi.nlm.nih.gov/34991070/ PAPMET Trial: Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed https://clinicaltrials.gov/ct2/show/NCT02761057 Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non–Clear-Cell Renal Cell Carcinoma and Genomic Correlates https://ascopubs.org/doi/10.1200/JCO.21.01944 Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605393/ Cabozantinib Plus Nivolumab Phase I Expansion Study in Patients With Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy https://aacrjournals.org/clincancerres/article/28/7/1353/682207/Cabozantinib-plus-Nivolumab-Phase-I-Expansion Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study https://ascopubs.org/doi/10.1200/JCO.21.00939 A Single-Arm, Multicenter, Phase 2 Study of Lenvatinib Plus Everolimus in Patients With Advanced Non–Clear Cell Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/33867192/ ESMO 2022 https://www.esmo.org/meetings/esmo-immuno-oncology-congress-2022/abstracts Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma. The SAVOIR Phase 3 Randomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2766797 SAMETA: An Open-Label, Three-Arm, Multicenter, Phase III Study of Savolitinib + Durvalumab Versus Sunitinib and Durvalumab Monotherapy in Patients With MET-Driven, Unresectable, Locally Advanced/Metastatic Papillary Renal Cell Carcinoma (PRCC). https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.TPS4601 A Phase II Trial of Doxorubicin and Gemcitabine in Renal Cell Carcinoma With Sarcomatoid Features: ECOG 8802 https://pubmed.ncbi.nlm.nih.gov/21298497/ A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 9ER) https://clinicaltrials.gov/ct2/show/NCT03141177

Dr Oh discusses the FDA approval of durvalumab plus gemcitabine and cisplatin in biliary tract cancer, the tolerability of the regimen, and the importance of using immunotherapy to treat this disease.

Discussion of a new, early phase clinical trial for patients with metastatic osteosarcoma targeting the DNA damage repair pathway. Dr. Vishu Avutu attained his M.D. from the University of Texas Southwestern Medical School and began his research endeavors with the Pediatric Oncology Education Program at St. Jude Children's Research Hospital; finding a passion for working with adolescents and young adults, Vishu matched to the internal medicine-pediatric residency at Harvard's Brigham and Women's/Boston Children's Hospitals. In addition to serving as Chief Resident, Vishu helped develop and launch the Center for Adolescent and Young Adult Oncology at the Dana Farber Cancer Institute. He then completed his medical oncology fellowship at Memorial Sloan Kettering Cancer Center. He is a co-founder of MSK's Adolescent and Young Adult Oncology Program, where his work has garnered MSK's Patient and Family Centered Care Grant Initiative and the Young Investigator Award from the American Society of Clinical Oncology. He is an assistant attending in the Departments of Medicine and Pediatrics and cares for AYAs with sarcomas.

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

Journal Review in HPB – Surgical Outcomes of the SWOG S1505 Trial Description: Neoadjuvant chemotherapy remains a controversial topic for resectable pancreatic adenocarcinoma. This randomized trial examines surgical and clinical outcomes from peri-operative regimens, mFOLFIRNOX and gem-Abraxane. The HPB Behind the Knife team dives into the specifics of the trial design and findings, as well as sits down with the Principal Investigator Dr. Syed Ahmad himself to ask about the behind-the-scenes decision-making and the investigations yet to come.  Links to Papers Reviewed in this Episode Surgical Outcome Results from SWOG S1505: A Randomized Clinical Trial of mFOLFIRINOX Versus Gemcitabine/Nab-paclitaxel for Perioperative Treatment of Resectable Pancreatic Ductal Adenocarcinoma Ann Surg. 2020 Sep;272(3):481-486 https://pubmed.ncbi.nlm.nih.gov/32740235/ Efficacy of Periopertive Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial JAMA Oncol. 2021 Mar;7(3):421-427 https://pubmed.ncbi.nlm.nih.gov/33475684/  Guest:  Syed Ahmad, MD (@SyedAAhmad5) is a Professor of Surgery and Chief of the Division of Surgical Oncology at the University of Cincinnati College of Medicine, and the Director of the UC Cancer Center. He is the surgical chair of SWOG, and a co-Principal Investigator of the SWOG S1505 study in addition to numerous other national trials for pancreatic cancer. 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 Center Other References from this Episode FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer N Engl J Med. 2018 Dec 20;379:2395-2406 https://www.nejm.org/doi/full/10.1056/NEJMoa1809775 APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma J Clin Oncol. 2019 May 20;37:no. 15 suppl:4000. https://ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.4000 Operative Standards in Cancer Surgery: Pancreatoduodenectomy: Superior Mesenteric Artery Dissection American College of Surgeons. 2020 Jun 18. https://www.facs.org/quality-programs/cancer/acs-crp/oscs https://www.youtube.com/watch?v=bs8xlCr5XyE The AHPBA Podcast  The Americas Hepato-Pancreato-Biliary Association https://podcasts.apple.com/us/podcast/the-ahpba-podcast/id1501441845   Please visit behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  

On this episode, we're reviewing recommendations from the International Association for the Study of Lung Cancer on the use of liquid biopsy for lung cancer. We'll also hear about a study that compared two regimens added to radiotherapy for pancreatic cancer.Coverage of stories discussed this week on ascopost.com:Consensus Statement From IASLC on Liquid Biopsy for Advanced NSCLCSBRT Plus Pembrolizumab/Trametinib vs Gemcitabine in Locally Recurrent Resected Pancreatic CancerTo listen to more podcasts from ASCO, visit asco.org/podcasts.

Featuring an interview with Dr Arjun Balar, including the following topics: Phase III VISION study: Lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (PC) (0:00) Updated safety outcomes from the EORTC 1333/PEACE III trial: Effect of adding bone-protecting agents (3:44) First results from the Phase III PEACE 1 study evaluating abiraterone acetate with prednisone and/or local radiation therapy for de novo metastatic castration-sensitive PC (5:09) Update on darolutamide tolerability: Outcomes with aggressive hormonal therapy for high-risk localized PC  (7:35) Bladder-sparing therapy with pembrolizumab, gemcitabine and concurrent hypofractionated radiation therapy for muscle-invasive bladder cancer (MIBC) (9:17) Results from the Phase II HCRN GU16-257 trial: Gemcitabine/cisplatin with nivolumab and selective bladder sparing for patients with MIBC (12:00) Long-term outcomes from the KEYNOTE-052 trial assessing first-line pembrolizumab for cisplatin-ineligible patients with advanced urothelial cancer (15:02) First-line maintenance therapy with avelumab for advanced urothelial cancer: Subgroup analysis of the JAVELIN Bladder 100 trial (17:19) Phase III CheckMate 9ER trial: Outcomes by baseline disease characteristics with nivolumab and cabozantinib for advanced renal cell carcinoma (RCC)  (18:29) Results from the Phase III KEYNOTE-564 study assessing pembrolizumab as postnephrectomy adjuvant therapy for patients with RCC  (20:16) Pembrolizumab with axitinib as first-line therapy for advanced RCC: Results from a 42-month follow-up of the KEYNOTE-426 trial (22:26) Updates on tyrosine kinase inhibitor and immune checkpoint inhibitor combination therapy and other novel agents for patients with RCC (24:07) Expert perspectives on advances in the treatment of genitourinary cancers (26:30) CME information and select publications

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  

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

In this episode, José Ignacio Nolazco, MD, and Alejandro Nolazco, MD, discuss in Spanish the latest immuno-oncology developments in the treatment of urothelial cancer from an Argentinian perspective.  Presenters:José Ignacio Nolazco, MD  Urology FollowHospital Universitario AustralBuenos Aires, ArgentinaAlejandro Nolazco, MDAssociate ProfessorDepartment of UrologyUniversidad Austral and Universidad Católica ArgentinaBuenos Aires, ArgentinaContent based on an online IME program supported by educational grants from EMD Serono, Inc and Pfizer.Link to full program, including associated downloadable slidesets and on-demand Webcast:https://bit.ly/3kJC5SL 

In this episode, Guiseppe Procopio, MD, and Cora N. Sternberg, MD, FACP, discuss in Italian the latest immuno-oncology developments in the treatment of urothelial cancer.  Presenters:Guiseppe Procopio, MD  Head of the Medical Oncology Genitourinary, Istituto Nazionale TumoriMedical OncologyFondazione IRCCS Istituto Nazionale dei TumoriMilan, ItalyCora N. Sternberg, MD, FACPProfessor of MedicineDepartment of Hematology/OncologyWeill Cornell MedicineNew York, New York, USAContent based on an online IME program supported by educational grants from EMD Serono, Inc and Pfizer.Link to full program, including associated downloadable slidesets and on-demand Webcast: http://bit.ly/3kJC5SL

Next up in the Foundations of #OncoPharm series, gemcitabine.

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)

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.

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

In this episode we question the conclusions of the phase II trial "Nab-Paclitaxel and Gemcitabine as First-line Treatment of Advanced or Metastatic Cholangiocarcinoma", review the long-term overall survival results from PALOMA-3, discuss Dr. Gyawali et al.'s paper on the need for transparency in reporting harms from cancer drugs, and interview Dr. Talal Hilal from the Scottsdale Mayo Clinic on his advice for trainees. Nab-paclitaxel and gemcitabine: doi.org/10.1001/jamaoncol.2018.3277 Palbociclib and fulvestrant: doi.org/10.1056/NEJMoa1810527 Reporting harms: doi.org/10.1136/bmj.k4383

Welcome back to this weekend's 2nd Cabral HouseCall! I'm so happy to have you back and we have more amazing community questions to answer, so let's get started! Paula: Hi doc. Very pleased with the info and insights discussed on your podcast. My question is in regards to chemotherapy. My father (61 yo) was diagnosed with a bladder tumor which was surgically removed 2 months ago. A week ago (without having fully recovered from the surgery and still using a catheter to urinate), he started a 6-cycle-long chemo protocol: Each cycle lasting 3 weeks with Gemcitabine 3x/cycle and Cisplatin 1x/cycle. Upon the first application of Cisplatin, the side effects were severe, ranging from headaches, to lack of appetite, weight loss, joint and back pain and constant nausea and brain fog. Needless to say, he dreads continuing treatment and has been following a low-carb diet when he does eat. We would like for him to go full-on ketogenic (based of Dr. Seifried's work) and compliment with other therapies. However, an alternative doc has advised us against STOPPING CHEMO and suggested we finish the 4-month-long treatment and then opt for other alternatives. We want to hear your take on this. Should he continue chemo given all those side effects? Or should we go the full-on functional route? Thanks a lot (I know this is a question with a long background info)   Jenett: Hi Dr. Cabral My question is regarding my four year old daughter. Her tongue has a white coating but I can see the red tastebuds through it like dots all over. She also has off and on itching in her vaginal area. I thought it was from her not wiping the area very well after peeing. I'm wondering if this is candida? If so, how do I treat it? Thank you for all you do! Jenett   Kristen: Hi Dr. Cabral, I've been listening to your podcast for about a year now and have learned so much in multiple areas thanks to your breadth of knowledge and desire to continue learning and educating others. As a Registered Dietitian, I'm also constantly trying to stay up on research but appreciate the more functional approach to medicine and have also gotten a health coaching certification so I can approach wellness a bit differently with some of my clients. However, my question today is in regards to myself. I'm a 29 year old relatively fit, recovering type-A female and over the past 2 years or so, have gone through quite a number of changes in my life - relationships, moving (states, towns, houses, etc), job changes, unemployment - and am finally in a bit of a more stable place, relatively speaking (relationship, home). I've never considered myself a highly anxious person but do now experience periods where it almost feels like a "butterflies in my stomach" sensation when my nerves are heightened or I'm anxious due to unknown circumstances/outcome. After learning more about normal bowel habits and healthy elimination, I realized that what I used to consider "normal" for myself was actually bordering on constipation and has since gotten worse this past year with so many life changes. Being a health professional who is highly interested in gut health, I'm seeing a possible connection between my changes in GI health and how these two might be correlated. Which leaves me wondering which angle to take in treating/resolving my issues. I've tried a range of approaches from probiotics and home-brewed kombucha to magnesium and now your digestive enzymes. I used to do smoothies almost daily but found that they didn't provide any sort of consistent relief or regularity for my situation. I know for some, they actually aren't the best solution when looking at digestive issues so I've currently made a switch away from them. Otherwise, I maintain a fairly healthy diet (with the occasional treats) which is mostly whole foods, plenty of fiber and at least 75 oz of water daily in addition to regular activity. I've tried a few unique approaches for a short time, never stuck with anything long term - very low carb for and also FODMAP (for a handful of days each), a detox/cleanse supplement regimen by NOW (coupled with flax, lemon, homemade green juice and mostly plant-based eating in addition to a less crazy schedule, I did see some regularity for a few days...a big change for me). But I don't want to mask symptoms that something is out of balance by taking supplements which make it seem as though things are functionally more optimally than they really are. Also, I should mention I've noticed heightened symptoms with my monthly cycle, specifically more breakouts, which I attribute to the hormone imbalance resulting from poor elimination. At this point, I'd say information overload or possibly analysis paralysis is what I'm suffering from and would love the opinion of an expert to narrow down my consideration for how to begin healing myself from this symptom. I'm ordering your HTMA test tonight as a good baseline to evaluate my current wellness and plan to use these results with other information in your reply. I greatly appreciate your time and experience in responding. Thanks SO MUCH for doing what you do. I'll continue to listen to each episode and share your wisdom with others it may help!! :)   Sheila: Hi Love your podcast, learn something every day. I am an active 62 year old but have noticed muscle loss especially in arms, help what can Indo to build up my muscles and stave off further decline?   Anonymous: Hi Dr. Cabral, Thank you for everything you're doing to help improve the life of others including myself. I have a few questions that i'm hoping you can help me with. first off, can candida transmitted through sexual intercourse or oral sex? I've had white sticky vaginal discharge and a thick white coating on my tongue(especially in the AM) for years. I have no idea what it is or how to get rid of it. I took your candida cleanse and am now taking the daily probiotics but it has not gone away. Can you give me some guidance on how to deal with this issue?   I hope hope you enjoyed this weekend's Cabral HouseCalls Q&A and all the tips we add in along the way! - - -  Show Notes & Resources: http://StephenCabral.com/590 - - - Get Your Question Answered: http://StephenCabral.com/askcabral  

Listen as Dr. Andrea Wang-Gillam explains standard dosing and delivery of gemcitabine/nab-paclitaxel in patients with pancreatic cancer.

John Neoptolomos discusses the ESPAC-4 trial, investigating a chemotherapy drug combination for patients with pancreatic cancer.

Prof Neoptolemos presents at ASCO 2016, a European phase III trial, one of the largest ever conducted in pancreatic cancer, which showed that adding the oral drug capecitabine chemotherapy to gemcitabine prolongs survival without increased toxicity.

Dr. Jack West, Swedish Cancer Institute, discusses current trials seeking to determine the efficacy of combining immunotherapy agents in lung cancer.

Dr. Jack West, Swedish Cancer Institute, discusses current trials seeking to determine the efficacy of combining immunotherapy agents in lung cancer.

Dr. Jack West, Swedish Cancer Institute, discusses current trials seeking to determine the efficacy of combining immunotherapy agents in lung cancer.

Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.

Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.

Dr. Jack West, Swedish Cancer Institute, reviews the choices for a first-line chemotherapy regimen based on a squamous histology.

Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.

Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.

Dr. Jack West, Swedish Cancer Institute, addresses the issue of choosing a first-line chemotherapy regimen based on an adenocarcinoma histology.

Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.

Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.

Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.

Dr. Heather Wakelee, Stanford University Medical Center, lists standard adjuvant chemotherapy regimens, comparing their administration and uses.

Dr. Heather Wakelee, Stanford University Medical Center, lists standard adjuvant chemotherapy regimens, comparing their administration and uses.

Dr. Heather Wakelee, Stanford University Medical Center, lists standard adjuvant chemotherapy regimens, comparing their administration and uses.

Dr. Nasser Hanna, Indiana University Health, lists chemo regiments appropriate for use with radiation in locally advanced NSCLC.