Ep. 86 Optimizing Treatment for Advanced HER2-Positive Upper GI Cancers with Dr. Geoffrey Buckle and Dr. Ronan Hsieh

"No cancer patient ever got healthier because their claim was denied and delayed," Mark Cuban says, and his answer is a contract that starts by trusting the doctor. On this episode of the BackTable Podcast, Dr. Ruchika Talwar, value-based care leader at Vanderbilt University Medical Center, talks with Mark Cuban, entrepreneur and founder of Mark Cuban Cost Plus Drug Company, about who actually sets the price of care in the United States. For oncology teams, he describes how an employer with access to its own claims data can contract directly with an oncology center for its employees with cancer. He also traces how a transparent pharmacy model led to Cost Plus Wellness, an open source library of direct contracts between self-insured employers and providers, and why he believes the contract, not the published price, is where the real problems hide. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction01:53 - From Drug Shortages to Cost Plus Drugs06:08 - Cost Plus Wellness and Direct Contracts11:04 - Publishing Provider Contracts16:39 - Using AI to Review Contracts and RFPs20:16 - Direct Contracting Advice for Hospitals and Physicians26:33 - Value-Based Care, Brokers, and Self-Insured Hospitals32:09 - Direct Contracting for Independent Practices34:20 - AI as a Business Adviser for Physicians38:39 - National Policy and Who Pays for Healthcare46:59 - Misaligned Incentives and Corporate Culture51:00 - Key Takeaways54:04 - Closing Remarks --- More about this episode The discussion then turns practical for physicians. Mark Cuban lays out how hospitals, clinics, and independent practices can find the self-insured employers among their own patients and offer direct contracts or carve-outs, why a promise to trust the doctor can earn employers a better rate, and how he runs contracts that stretch past a thousand pages through several AI models in turn. He and Dr. Talwar also cover what employers can learn from Form 5500 filings, the national changes he would make, from ending gag clauses to standardized public contracts, and why both see misaligned incentives as the root of the problem. --- Resources Mark Cuban Cost Plus Drug Companyhttps://costplusdrugs.com Cost Plus Wellness: an open source initiative by Mark Cubanhttps://costpluswellness.com Mark Cuban dives into direct contracting. Becker's Hospital Review. 2026https://www.beckershospitalreview.com/finance/mark-cuban-dives-into-direct-hospital-contracting/ Form 5500 filings search (EFAST2), U.S. Department of Laborhttps://www.efast.dol.gov/welcome.html KFF. 2025 Employer Health Benefits Surveyhttps://www.kff.org/health-costs/2025-employer-health-benefits-survey/ Gag Clause Prohibition Compliance Attestation. Centers for Medicare & Medicaid Serviceshttps://www.cms.gov/marketplace/about/oversight/other-insurance-protections/gag-clause-prohibition-compliance-attestation New generic drug company named after Mark Cuban first founded by a part-time radiologist. Health Imaging https://healthimaging.com/topics/healthcare-management/medical-practice-management/mark-cuban-generic-drug-company --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

A drug that nearly doubles overall survival in metastatic pancreatic cancer is something Dr. Arsen Osipov says the field has never seen before, and it is why he calls the pan-RAS inhibitor daraxonrasib a paradigm shift on the scale of the first immunotherapy approvals. On this episode of the BackTable GI Oncology Creator Weekend™, host Dr. Andrew Hendifar leads a tumor board on metastatic pancreatic cancer with fellow GI oncologists Dr. Arsen Osipov and Dr. Daniel Ahn. They start with the workup. A CT of the chest, abdomen, and pelvis is usually enough, and a PET rarely changes management. They also cover what to do when a patient does not make CA 19-9, the debate over routine DPYD testing before 5-FU, and why every patient gets molecular profiling. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction01:53 - Workup and Staging in Metastatic Pancreatic Cancer04:33 - Blood Work, CA 19-9, and DPYD Testing08:46 - Molecular Profiling: Blood Versus Tissue11:29 - Choosing First-Line Chemotherapy for Fit and Frail Patients14:19 - Pain, Anorexia, and Cachexia17:47 - RASolute 302 and Daraxonrasib20:50 - A Future Without Chemotherapy?22:17 - Variant-Specific Versus Pan-RAS Inhibitors and Resistance26:43 - KRAS Trials to Watch and Treatment After Progression29:57 - Beyond RAS: Immunotherapy and MEK Inhibition31:04 - Case: BRAF V600E and ctDNA Surveillance36:22 - Closing Remarks --- More about this episode Next, they compare first-line options (modified FOLFIRINOX, NALIRIFOX, and gemcitabine with nab-paclitaxel), talk through how to counsel a frail patient in their eighties, and share how they manage pain, appetite loss, and cachexia. The second half turns to KRAS: the RASolute 302 results, how pan-RAS and variant-specific inhibitors differ, early signs of resistance, and whether chemotherapy still has a future in this disease. They close with a BRAF V600E case in which a rising circulating tumor DNA signal, five years after surgery, prompted closer surveillance. --- Resources FDA approves daraxonrasib for metastatic pancreatic adenocarcinoma (August 2026)https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daraxonrasib-metastatic-pancreatic-adenocarcinoma Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer. N Engl J Med. 2026https://doi.org/10.1056/NEJMoa2505783 FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer (PRODIGE 4/ACCORD 11). N Engl J Med. 2011https://pubmed.ncbi.nlm.nih.gov/21561347/ NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3). Lancet. 2023https://pubmed.ncbi.nlm.nih.gov/37708904/ Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine (MPACT). N Engl J Med. 2013https://pubmed.ncbi.nlm.nih.gov/24131140/ Ponsegromab for the Treatment of Cancer Cachexia. N Engl J Med. 2024https://doi.org/10.1056/NEJMoa2409515 Daraxonrasib Nearly Doubles Survival in Previously Treated Metastatic Pancreatic Cancer (RASolute 302). The ASCO Post. June 2026https://ascopost.com/news/june-2026/daraxonrasib-nearly-doubles-survival-in-previously-treated-metastatic-pancreatic-cancer/ Dr. Daniel Ahn, Mayo Clinic physician profilehttps://www.mayoclinic.org/biographies/ahn-daniel-h-d-o/bio-20235148 --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

Most patients with localized pancreatic cancer already have disease the scans cannot see, which is why these GI oncologists treat chemotherapy before surgery as a test of tumor biology. On this episode of the BackTable GI Oncology Creator Weekend™, medical oncologist Dr. Andrew Hendifar leads a tumor board with GI medical oncologists Dr. Arsen Osipov and Dr. Daniel Ahn on the perioperative management of pancreatic cancer. They explain why nearly every patient with localized disease now starts with chemotherapy rather than surgery, which red flags such as an elevated CA 19-9, enlarged lymph nodes, or profound weight loss point to hidden micrometastatic disease, and why an 80-year-old can still be a candidate for FOLFIRINOX when biological age outweighs chronological age. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction01:11 - Workup and Resectability in Localized Pancreatic Cancer05:14 - Upfront Surgery and Screening High-Risk Patients09:04 - Choosing and Timing Neoadjuvant Chemotherapy13:20 - Adjuvant Chemotherapy and Pathologic Response17:32 - Supportive Care, Prehabilitation, and Community Practice22:14 - RAS Inhibitors in the Adjuvant Setting26:04 - Circulating Tumor DNA (ctDNA) Surveillance28:56 - Case: Locally Advanced Pancreatic Cancer34:32 - Closing Remarks --- More about this episode The conversation moves through restaging every two months, why about four months of chemotherapy before surgery has become the norm with the rest of six months given afterward, and why a poor pathologic response rarely prompts a change in regimen. Dr. Osipov and Dr. Ahn make the case for early dietitian involvement, pancreatic enzyme replacement, and prehabilitation, share practical advice for community oncologists, and discuss the RASolute 304 trial of an adjuvant RAS inhibitor, the open question of resistance, and where circulating tumor DNA does and does not guide decisions. They close with a case of locally advanced disease encasing the superior mesenteric artery, treated with modified FOLFIRINOX and then radiation, in a patient now about a year and a half past radiation and doing well. --- Resources Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer (Alliance A021806, perioperative versus adjuvant chemotherapy, trial record NCT04340141)https://clinicaltrials.gov/study/NCT04340141 FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer (PRODIGE 24). N Engl J Med. 2018https://pubmed.ncbi.nlm.nih.gov/30575490/ Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4). Lancet. 2017https://pubmed.ncbi.nlm.nih.gov/28129987/ Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial (APACT). J Clin Oncol. 2023https://pubmed.ncbi.nlm.nih.gov/36521097/ NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3). Lancet. 2023https://pubmed.ncbi.nlm.nih.gov/37708904/ Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas (Alliance A021501). JAMA Oncol. 2022https://pubmed.ncbi.nlm.nih.gov/35834226/ RASolute 304: Adjuvant Daraxonrasib Versus Standard of Care Observation in Resected Pancreatic Ductal Adenocarcinoma (trial record NCT07252232)https://clinicaltrials.gov/study/NCT07252232 FDA approves daraxonrasib for metastatic pancreatic adenocarcinoma (August 2026)https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daraxonrasib-metastatic-pancreatic-adenocarcinoma Pancreatic Cancer Multidisciplinary Clinic, Cedars-Sinaihttps://www.cedars-sinai.org/stories-and-insights/healthy-living/pancreatic-cancer-clinic-saves-time-and-lives Dr. Daniel Ahn, Mayo Clinic physician profilehttps://www.mayoclinic.org/biographies/ahn-daniel-h-d-o/bio-20235148 --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

Few oncologists know neuroendocrine tumors from both sides of the exam table: first as a patient diagnosed during training, and now as the doctor treating them. This physician brings both perspectives to one pressing question: when a tumor progresses on a somatostatin analog, what comes next? On this episode of BackTable Tumor Board, Dr. Aman Chauhan, a medical oncologist at UCSF, interviews Dr. Mark Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, about treatment strategies for advanced neuroendocrine tumors beyond first-line therapy. They start with what progression on a somatostatin analog really means, how grade, Ki-67, primary site, and the pace of liver disease shape the next step, and why observation is sometimes the right call. Dr. Lewis explains how he sets expectations for PRRT after NETTER-1 and NETTER-2, including the small but real risk of secondary myelodysplasia and leukemia. --- Get the BackTable apphttps://www.backtable.com/app --- This podcast is supported by Exelixishttps://www.exelixis.com/ --- Timestamps 00:00 - Introduction02:22 - Progression on a Somatostatin Analog05:34 - Tumor Biology, Grade, and Observation12:51 - Somatostatin Analogs and Carcinoid Syndrome18:50 - PRRT After NETTER-1 and NETTER-225:56 - Chemotherapy Versus Targeted Therapy32:35 - The CABINET Trial and Cabozantinib38:39 - Dosing and Toxicity of Oral Therapy43:57 - Liver-Directed Therapy and Rebiopsy48:08 - Future Trials and Alpha Emitters50:47 - When to Stop Somatostatin Analogs54:27 - Practice-Changing Trials and Sequencing Lessons59:25 - Closing Remarks --- More about this episode The conversation then turns to systemic therapy: where capecitabine and temozolomide still fit, the trade-offs of earlier targeted agents, and the inclusive design of the CABINET trial of cabozantinib in pancreatic and extra-pancreatic NETs. Dr. Lewis describes why an oral therapy matters for rural patients who cannot easily reach a center that offers PRRT, and both doctors share how they dose oral therapy and watch for early toxicity. They close with when to rebiopsy a disease that is changing, alpha emitters on the horizon, when to stop a somatostatin analog, and the sequencing mistake Dr. Lewis most wants listeners to avoid: doing something because you can rather than because you should. --- Resources Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors (CABINET). N Engl J Med. 2025https://pubmed.ncbi.nlm.nih.gov/39282913/ FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET (March 2025)https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-adults-and-pediatric-patients-12-years-age-and-older-pnet-and-epnet Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors (NETTER-1). N Engl J Med. 2017https://pubmed.ncbi.nlm.nih.gov/28076709/ Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide in newly diagnosed, advanced grade 2-3, well-differentiated GEP-NETs (NETTER-2). Lancet. 2024https://pubmed.ncbi.nlm.nih.gov/38851203/ Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE). Lancet. 2026https://pubmed.ncbi.nlm.nih.gov/42392118/ Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211). J Clin Oncol. 2023https://pubmed.ncbi.nlm.nih.gov/36260828/ Everolimus for Advanced Pancreatic Neuroendocrine Tumors (RADIANT-3). N Engl J Med. 2011https://pubmed.ncbi.nlm.nih.gov/21306238/ Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. N Engl J Med. 2011https://pubmed.ncbi.nlm.nih.gov/21306237/ Treatment of the Malignant Carcinoid Syndrome: Evaluation of a Long-Acting Somatostatin Analogue. N Engl J Med. 1986https://pubmed.ncbi.nlm.nih.gov/2427948/ Moertel CG. Karnofsky Memorial Lecture: An Odyssey in the Land of Small Tumors. J Clin Oncol. 1987https://pubmed.ncbi.nlm.nih.gov/2443618/ Lower or Standard Dose Regorafenib in Refractory Metastatic Colorectal Cancer (ReDOS, trial record)https://clinicaltrials.gov/study/NCT02368886 Dr. Aman Chauhan, UCSF Health physician profilehttps://www.ucsfhealth.org/providers/aman-chauhan Dr. Mark Lewis, Intermountain Health physician profilehttps://doctors.intermountainhealth.org/provider/mark-a-lewis/2558622 --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

Five years ago, first-line treatment for advanced HER2-negative gastroesophageal cancer meant chemotherapy; today claudin 18.2, PD-L1, and mismatch repair status shape the plan, often for a patient who cannot afford to wait for the results. On this episode of the BackTable GI Oncology Creator Weekend™, host Dr. Kate Baker interviews medical oncologists Dr. Ronan Hsieh and Dr. Dani Castillo about the diagnosis and management of advanced HER2-negative upper GI cancers. They discuss the biomarker workup at diagnosis, next-generation sequencing and liquid biopsy, when to biopsy metastatic sites, and why both guests start chemotherapy before every result is available. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction01:32 - Diagnosis and Biomarker Testing04:25 - Circulating Tumor DNA 06:31 - Starting Chemotherapy Before Biomarker Results09:10 - First-Line Therapy and Zolbetuximab Toxicity14:46 - Sequencing Therapy in Double Expressors21:11 - Clinical Trials and Emerging Targets24:54 - Immunotherapy Eligibility and Autoimmune Disease29:26 - Obstruction, Bleeding, and Multidisciplinary Care32:30 - Supportive Care36:50 - Future Directions39:36 - Organ Preservation and Closing Remarks --- More about this episode The conversation covers first-line therapy based on the SPOTLIGHT, GLOW, and CheckMate 649 trials, practical strategies for the nausea and vomiting that come with zolbetuximab, and how to sequence treatment when a tumor is positive for both claudin 18.2 and PD-L1, including the ILUSTRO cohort 4 data and the ongoing LUCERNA trial. Dr. Hsieh and Dr. Castillo make the case for offering clinical trials early, discuss immunotherapy in patients with autoimmune disease, and explain how stents, feeding tubes, and palliative radiation help manage obstruction and bleeding. They close on supportive care, from palliative medicine and dietitians to social work and psycho-oncology, and on organ preservation in mismatch repair-deficient disease, a reminder that caring for these patients takes a whole team. --- Resources Zolbetuximab plus mFOLFOX6 in CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT). Lancet. 2023https://pubmed.ncbi.nlm.nih.gov/37068504/ Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023https://pubmed.ncbi.nlm.nih.gov/37524953/ Impact and effective management of nausea/vomiting on patients treated with zolbetuximab + chemotherapy: insights from the phase III SPOTLIGHT and GLOW studies. ESMO Open. 2026https://pubmed.ncbi.nlm.nih.gov/41741112/ First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649). Lancet. 2021https://pubmed.ncbi.nlm.nih.gov/34102137/ First-line zolbetuximab plus mFOLFOX6 and nivolumab in unresectable CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial (ILUSTRO cohort 4). Nat Med. 2026https://pubmed.ncbi.nlm.nih.gov/41840238/ Zolbetuximab plus pembrolizumab and chemotherapy in CLDN18.2-positive, HER2-negative, PD-L1-positive gastric or gastroesophageal junction adenocarcinoma: randomized, double-blind, phase III LUCERNA trial. ESMO Gastrointest Oncol. 2026https://pubmed.ncbi.nlm.nih.gov/42583212/ LUCERNA trial record (NCT06901531)https://clinicaltrials.gov/study/NCT06901531 Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023https://pubmed.ncbi.nlm.nih.gov/37871604/ OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer. J Clin Oncol. 2006https://pubmed.ncbi.nlm.nih.gov/16421419/ Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol. 2009https://pubmed.ncbi.nlm.nih.gov/19786657/ Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: the INFINITY study by GONO. Ann Oncol. 2025https://pubmed.ncbi.nlm.nih.gov/39637944/ Dr. Ronan Hsieh, Swedish physician profilehttps://www.swedish.org/doctors/medical-oncology/wa/seattle/ronan-hsieh-1457880031 Dr. Dani Castillo, medical oncology, City of Hopehttps://www.cancercenter.com/physician-directory/dani-castillo Dr. Kate Baker, BackTable Tumor Board contributor pagehttps://www.backtable.com/shows/tumor-board/contributors/dr-kate-baker --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

When a gastroesophageal tumor is positive for HER2, PD-L1, and claudin 18.2, which target should you treat first and how do you decide? On this episode of the BackTable GI Oncology Creator Weekend™, host Dr. Kate Baker interviews Dr. Geoffrey Buckle, a GI medical oncologist at UCSF, and Dr. Ronan Hsieh, a GI oncologist at Swedish Cancer Institute in Seattle, for a breakdown of therapy selection and management in advanced HER2-positive upper GI cancers. They start with a detailed case, covering biomarker workup, how to choose a first-line regimen without head-to-head data, and how to manage nutrition and palliative radiation when a patient presents with dysphagia and weight loss. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction01:41 - Case Presentation and Biomarker Workup05:07 - First-Line Treatment Selection11:27 - Oligoprogressive Disease and Local Therapy16:02 - HER2 Testing and Tumor Heterogeneity20:19 - ctDNA in Upper GI Cancers22:27 - HERIZON-GEA-01 and Zanidatamab27:18 - Triplet Versus Doublet and Diarrhea Management29:17 - Second-Line Therapy and Rebiopsy32:33 - Trastuzumab Deruxtecan and Interstitial Lung Disease36:33 - Later-Line Options and HER2-Low Disease39:17 - Future Directions and Closing Remarks --- More about this episode The conversation expands to interpreting equivocal HER2 results, tumor heterogeneity, and the importance of a second pathology review before committing to a treatment strategy. Dr. Hsieh explains how he approaches the HERIZON-GEA-01 trial data and the need to manage triplet therapy toxicity, especially diarrhea. The group discusses second-line rebiopsy to confirm HER2 status, the role of circulating tumor DNA (ctDNA), counseling and monitoring for interstitial lung disease on antibody-drug conjugates, and what to do for HER2 IHC 2+ FISH-negative tumors. They close with future directions, including trials moving HER2-directed therapies into earlier disease, the challenge of limited therapy lines, and why every line counts in this patient population. --- Resources Shitara K, et al. Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer (HERIZON-GEA-01). N Engl J Med. 2026https://pubmed.ncbi.nlm.nih.gov/42202319/ FDA approves zanidatamab-hrii and tislelizumab-jsgr for HER2-positive gastric, gastroesophageal junction and esophageal adenocarcinoma (August 2026)https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanidatamab-hrii-and-tislelizumab-jsgr-her2-positive-gastric-gastroesophageal-junction Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023https://pubmed.ncbi.nlm.nih.gov/37871604/ Trastuzumab in combination with chemotherapy versus chemotherapy alone for HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA). Lancet. 2010https://pubmed.ncbi.nlm.nih.gov/20728210/ Trastuzumab Deruxtecan in HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial (DESTINY-Gastric01). J Clin Oncol. 2023https://pubmed.ncbi.nlm.nih.gov/36379002/ GEMINI-PeriOp GC: Novel Agents or Combinations as Perioperative Treatment in Locally Advanced Resectable Gastroesophageal Adenocarcinoma (trial record)https://clinicaltrials.gov/study/NCT07069712 Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023https://pubmed.ncbi.nlm.nih.gov/37524953/ Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer (MATTERHORN). N Engl J Med. 2025https://pubmed.ncbi.nlm.nih.gov/40454643/NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer and Esophageal and Esophagogastric Junction Cancers (current versions)https://www.nccn.org/guidelines/category_1Dr. Geoffrey Buckle, UCSF Health physician profilehttps://www.ucsfhealth.org/providers/geoffrey-buckle Dr. Ronan Hsieh, Swedish physician profilehttps://www.swedish.org/doctors/medical-oncology/wa/seattle/ronan-hsieh-1457880031 Dr. Kate Baker, BackTable Tumor Board contributor pagehttps://www.backtable.com/shows/tumor-board/contributors/dr-kate-baker --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

How do you choose between perioperative chemotherapy and trimodality therapy for a patient with localized upper GI cancer, and what has the newest data actually settled? On this episode of BackTable Tumor Board, host Dr. Kate Baker interviews Dr. Dani Castillo, a medical oncologist at City of Hope in Duarte, California, and Dr. Alexandra Gangi, a gastrointestinal surgical oncologist at Cedars-Sinai in Los Angeles, about everything that happens between a new diagnosis and a resection in localized esophageal, gastroesophageal junction and gastric cancer. They cover diagnostic workup, Siewert classification, staging laparoscopy, histology, biomarker testing, surgical candidacy, and the challenges of nutrition and prehabilitation. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction01:42 - Diagnostic Workup and Siewert Classification04:20 - Histology, Risk Stratification, and Biomarkers07:03 - Surgical Candidacy and Preoperative Optimization10:26 - Perioperative Chemotherapy versus Trimodality Therapy13:37 - Chemotherapy Tolerability, Immunotherapy, and Dose Reduction15:10 - Gastrectomy, Esophagectomy, and Recovery20:05 - Pathologic Response and Adjuvant Decisions21:55 - Organ Preservation and ctDNA24:54 - Future Directions and Ongoing Trials26:35 - Multidisciplinary Care and Community Practice27:40 - Closing Remarks --- More about this episode The conversation tackles the choice between perioperative chemotherapy and chemoradiation, when to add immunotherapy, and the latest data from ESOPEC and MATTERHORN. Dr. Gangi explains why subtotal versus total gastrectomy, anastomotic technique, and node dissection matter for recovery. The team discusses the role of organ preservation, ctDNA for de-escalation, and why multidisciplinary care remains essential even in smaller community practices. The episode closes with real-world strategies for managing frailty, dose reduction, and ensuring patients and providers are aligned before heading to the OR and why upper GI cancer stays a multidisciplinary disease even where the team is small. --- Resources Hoeppner J, et al. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer (ESOPEC). N Engl J Med. 2025https://pubmed.ncbi.nlm.nih.gov/39842010/ ESOPEC trial registry record (NCT02509286)https://clinicaltrials.gov/study/NCT02509286 Al-Batran SE, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin (FLOT4). Lancet. 2019https://pubmed.ncbi.nlm.nih.gov/30982686/ Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN). Lancet. 2026https://pubmed.ncbi.nlm.nih.gov/42716074/ MATTERHORN trial registry record (NCT04592913)https://clinicaltrials.gov/study/NCT04592913 Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of KEYNOTE-585. J Clin Oncol. 2025https://pubmed.ncbi.nlm.nih.gov/40829093/ KEYNOTE-585 trial registry record (NCT03221426)https://clinicaltrials.gov/study/NCT03221426 Goodman KA, et al. Randomized Phase II Study of PET Response-Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial. J Clin Oncol. 2021https://pubmed.ncbi.nlm.nih.gov/34077237/ CALGB 80803 trial registry record (NCT01333033)https://clinicaltrials.gov/study/NCT01333033 Kelly RJ, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer (CheckMate 577). N Engl J Med. 2021https://pubmed.ncbi.nlm.nih.gov/33789008/ Cunningham D, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer (MAGIC). N Engl J Med. 2006https://pubmed.ncbi.nlm.nih.gov/16822992/ NCCN Guidelines Insights: Esophageal and Esophagogastric Junction Cancers, Version 4.2026. J Natl Compr Canc Netw. 2026https://pubmed.ncbi.nlm.nih.gov/42753809/ NCCN Clinical Practice Guidelines in Oncology, treatment by cancer typehttps://www.nccn.org/guidelines/category_1 Genomics of gastroesophageal junction adenocarcinomas and the Siewert classification. Transl Gastroenterol Hepatol. 2026https://pubmed.ncbi.nlm.nih.gov/42291157/ Dr. Dani Castillo, medical oncology, City of Hopehttps://www.cancercenter.com/physician-directory/dani-castillo Dr. Alexandra Gangi, Cedars-Sinai faculty profilehttps://researchers.cedars-sinai.edu/Alexandra.Gangi Dr. Alexandra Gangi, NANETS Board of Directors profilehttps://nanets.net/about/board-of-directors/450-gangi Dr. Kate Baker, BackTable contributor pagehttps://www.backtable.com/shows/tumor-board/contributors/dr-kate-baker --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

What options remain when a patient with microsatellite stable metastatic colorectal cancer (MSS mCRC) has progressed through every standard line of chemotherapy? On this episode of BackTable Tumor Board, Dr. Jun Gong is joined by Dr. Ibrahim Sahin and Dr. Sandra Algaze to explore the nuances of late-line management in MSS-mCRC. They discuss how to approach oxaliplatin retreatment and anti-EGFR rechallenge, the growing role of liquid biopsy and biomarker-driven selection, and the practicalities of DPYD testing after recent guideline changes. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction01:55 - Oxaliplatin Retreatment and Anti-EGFR Rechallenge07:53 - DPYD Testing and Liquid Biopsy14:00 - Comparing Rechallenge and Conventional Agents15:42 - STELLAR-303 and Third-Line Options22:53 - Immunotherapy and MSS Biology25:42 - SUNLIGHT, FRESCO-2, and CORRECT Trials30:41 - Alternative Dosing Strategies32:02 - Botensilimab and Balstilimab Update37:06 - Neoadjuvant Immunotherapy38:15 - Emerging Antibody-Drug Conjugates 42:02 - Closing Remarks --- More about this episode The conversation walks through the latest clinical trial results for third-line and beyond, including strategies for dosing and tolerability, and the unique challenges posed by liver metastases. Drs. Sahin and Algaze highlight new developments in immunotherapy, antibody-drug conjugates, and bispecific antibodies, as well as the importance of matching therapy to both tumor biology and patient needs. They close with insights on patient monitoring, toxicity management, and the value of multidisciplinary care for this complex population. --- Resources STELLAR-303: Zanzalintinib Plus Atezolizumab Versus Regorafenib in Refractory Colorectal Cancer (The Lancet)https://pubmed.ncbi.nlm.nih.gov/41130252/ SUNLIGHT: Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer (NEJM)https://www.nejm.org/doi/full/10.1056/NEJMoa2214963 FRESCO-2: Fruquintinib Versus Placebo in Refractory Metastatic Colorectal Cancer (The Lancet)https://www.thelancet.com/article/S0140-6736(23)00772-9/abstract CAPRI-2 GOIM: Liquid Biopsy Genomic Profiling to Predict FOLFIRI Plus Cetuximab Efficacy (ESMO Open)https://www.esmoopen.com/article/S2059-7029(25)00380-1/fulltext Botensilimab Plus Balstilimab in Relapsed/Refractory MSS Metastatic Colorectal Cancer (Nature Medicine)https://www.nature.com/articles/s41591-024-03083-7 Phase I Study of Telisotuzumab Adizutecan (ABBV-400), a c-Met Antibody-Drug Conjugate, in Late-Line Colorectal Cancer (JCO)https://ascopubs.org/doi/10.1200/JCO-25-01525 --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

Which molecular alterations in colorectal cancer now change treatment and how quickly do you need the results to make the right call? On this episode of BackTable Tumor Board, Dr. Jun Gong interviews Dr. Ibrahim Sahin and Dr. Sandra Algaze about the latest advances in molecular-driven therapy across adjuvant and metastatic settings. They cover aspirin in PI3K-altered disease, the shift toward early next-generation sequencing, and the operational realities of systematic profiling at diagnosis. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction07:50 - BREAKWATER and First-Line BRAF Therapy13:00 - Biomarker Turnaround and Systematic Profiling17:58 - MSI-High Disease and Immunotherapy Trials21:54 - Anti-PD-1 vs Anti-PD-L1 in CRC25:17 - Doublet vs Single-Agent Immunotherapy27:41 - KRYSTAL-10 and KRAS G12C Inhibition33:34 - Anti-EGFR Sequencing and CR-SEQUENCE38:47 - New Targets and Emerging Therapies43:02 - Closing Remarks --- More about this episode The discussion moves from first-line BRAF and MSI-high options to anti-EGFR sequencing, ctDNA hyperselection, and the nuances of chemotherapy backbone choice. Drs. Sahin and Algaze review new trial data including BREAKWATER, KEYNOTE-177, CheckMate 8HW, KRYSTAL-10, and CR-SEQUENCE, highlight the promise and pitfalls of targeted strategies, and close with a look at emerging therapies and the multidisciplinary teamwork needed to match biology to treatment. --- Resources ALASCCA: Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer (NEJM)https://www.nejm.org/doi/full/10.1056/NEJMoa2504650 BREAKWATER: Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer (NEJM)https://www.nejm.org/doi/full/10.1056/NEJMoa2501912 COMMIT (NRG-GI004 / SWOG-S1610): Atezolizumab Monotherapy vs mFOLFOX6/Bevacizumab/Atezolizumab in dMMR/MSI-H mCRChttps://clinicaltrials.gov/study/NCT02997228 CheckMate 8HW: Nivolumab Plus Ipilimumab Versus Nivolumab in MSI-High Metastatic Colorectal Cancer (The Lancet)https://pubmed.ncbi.nlm.nih.gov/39874977/ KRYSTAL-10: Adagrasib Plus Cetuximab Versus Chemotherapy in Previously Treated KRAS G12C-Mutated Colorectal Cancerhttps://clinicaltrials.gov/study/NCT04793958 CR-SEQUENCE: Anti-EGFR Versus Anti-VEGF Sequencing in RAS Wild-Type Left-Sided mCRC (ASCO 2026 Abstract)https://ascopubs.org/doi/10.1200/JCO.2026.44.16_suppl.3512 --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

How much of perioperative colorectal cancer management has changed in just one year, and what does it mean for patient care? On this episode of BackTable Tumor Board, Dr. Jun Gong is joined by Dr. Ibrahim Sahin and Dr. Alexandra Gangi to review the latest practice-changing data in colon and rectal cancer. They discuss observation versus maintenance immunotherapy in MSI-high disease, the CHALLENGE trial's surprising results on exercise and disease-free survival, and the evolving role of ctDNA and local therapies after liver metastasis resection. The conversation also covers adjuvant immunotherapy duration, comparing microwave ablation with SBRT, and how molecular residual disease (MRD) can guide post-resection decisions. They walk through a complex case of liver metastases, highlight the use of hepatic arterial infusion pumps, and discuss the future of transplant for unresectable disease. The discussion closes with practical advice on patient selection, multidisciplinary care, and the ongoing need for consensus as new therapies and biomarkers emerge. --- Get the BackTable apphttps://www.backtable.com/app --- Timestamps 00:00 - Introduction05:29 - Monotherapy, Doublet, and Treatment Duration10:35 - CHALLENGE Trial and Exercise After Surgery16:18 - Adjuvant Immunotherapy and Liver Metastases23:39 - ctDNA and Molecular Residual Disease29:44 - Case: Unresectable Liver Metastases and HAI Pump39:17 - Closing Thoughts --- Resources CHALLENGE Trial: Structured Exercise after Adjuvant Chemotherapy for Colon Cancerhttps://pubmed.ncbi.nlm.nih.gov/40450658/ ATOMIC Trial (Alliance A021502): Atezolizumab plus FOLFOX for Stage III Mismatch Repair Deficient Colon Cancerhttps://pubmed.ncbi.nlm.nih.gov/41880612/ Phase 2 LAVA-CRLM Trial: Microwave Ablation versus SBRT for Colorectal Liver Metastaseshttps://clinicaltrials.gov/study/NCT03654131 COLLISION Trial: Thermal Ablation versus Surgical Resection of Small-Size Colorectal Liver Metastaseshttps://pubmed.ncbi.nlm.nih.gov/39848272/ --- BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app