S18 Ep47: Dissecting Diagnostic and Management Factors in Systemic Mastocytosis

In today’s episode, we welcomed Tracy I. George, MD, who provided a pathologist’s perspective on the diagnosis and evolving management considerations for systemic mastocytosis. Dr George is president of the Innovation Business Unit and chief scientific officer at ARUP Laboratories and a professor of pathology at the Spencer Fox Eccles School of Medicine at the University of Utah in Salt Lake City.In the exclusive interview, Dr George highlighted the key hallmarks of systemic mastocytosis that can inform diagnosis, detailed how pathologists collaborate with other multidisciplinary experts to care for patients with systemic mastocytosis, and explained how agents such as avapritinib (Ayvakit) and bezuclastinib (CGT9486) are transforming patient care.

In today’s episode, we spoke with Elias Jabbour, MD, and Dennis Kim, MD. Dr Jabbour is a professor of Leukemia at The University of Texas MD Anderson Cancer Center in Houston. Dr Kim is an associate professor at the Institute of Medical Science at the University of Toronto in Canada.In our exclusive interview, Drs Jabbour and Kim discussed the third-generation TKI olverembatinib (HQP1351), how it works, and its advantages compared with other treatment options for chronic myeloid leukemia and acute lymphoblastic leukemia. Additionally, the 2 experts overviewed data for the investigational TKI that came out of the 2026 ASCO Annual Meeting like the phase 1b HQP1351CU101 trial (NCT04260022) and a single-arm, multicenter study (ChiCTR2200061655), as well as the next steps for olverembatinib like in the ongoing phase 3 POLARIS-2 (NCT06423911) trial.

Highlights from the PER® CME activity "Advancing Targeted Therapy in HR+/HER2– Metastatic Breast Cancer: Integrating Next-Generation Endocrine and PAM-Pathway Strategies Into Practice" — this podcast is not certified for credit. To participate in the full accredited activity and earn CME credit, use the link below.In this podcast, experts Joyce O’Shaughnessy, MD, Sarat Chandarlapaty, MD, PhD, Mitchell Elliott, MD, FRCPC, and Seth A. Wander, MD, PhD, discuss how they are integrating recent data from pivotal clinical trials evaluating next-generation oral selective estrogen receptor degraders (SERDs) as well as inhibitors of the PI3K/AKT/mTOR signaling pathway into the management of patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC), using a variety challenging clinical scenarios to draw out insights and clinical pearls.Earn CME credit by completing the full accredited activity (available through July 31, 2027): https://www.gotoper.com/courses/advancing-targeted-therapy-in-hrher2-metastatic-breast-cancer-integrating-next-generation-endocrine-and-pam-pathway-strategies-into-practiceThis podcast, including the narration, was developed by PER® (Physicians’ Education Resource®, LLC) editorial staff from the full online CME activity developed with these faculty. The narration was voiced by a PER staff member or by an AI tool. The podcast contains no product advertising. The full activity is supported by educational grants from Lilly; Rigel Pharmaceuticals; and Stemline Therapeutics, Inc.This content is for educational purposes only and is not a substitute for the independent clinical judgment of a health care professional. Faculty may discuss investigational or off-label uses; consult prescribing information for any products discussed.

In today’s episode, we spoke with Philip A. Philip, MD. Dr Philip is the director of Gastrointestinal Oncology, co-director of the Pancreatic Cancer Center, and medical director of Research and Clinical Care Integration at the Henry Ford Cancer Institute in Detroit, Michigan.In our exclusive interview, Dr Philip discussed the February 2026 FDA approval of Optune Pax for lo cally advanced pancreatic cancer in addition to key data from the phase 3 PANOVA-3 trial (NCT03377491), which evaluated the modality in combination with gemcitabine and nab-paclitaxel (Abraxane) in this population. Philip looked ahead toward combination regimens with newly approved drugs like daraxonrasib (Rasonque).

In this episode of Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Pashtoon Kasi, MD, MS, the medical director of GI Medical Oncology, the Rad Family Chair in Gastrointestinal Oncology, and an associate clinical professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Orange County in Irvine, California.Their discussion centered on the rapid rise of neoadjuvant immunotherapy in colorectal cancer (CRC) management, framing the shift in which immunotherapy is given upfront and surgery becomes the adjuvant step as a genuine paradigm change. Drs Park and Kasi grounded the conversation in the biology of mismatch repair–deficient (dMMR)/microsatellite instability–high tumors, which harbor a high neoantigen load, rendering them sensitive to checkpoint blockade.A major focus was the treatment evolution that stemmed from data from the phase 3 ATOMIC trial (NCT02912559), which added atezolizumab (Tecentriq) to FOLFOX (leucovorin, fluorouracil, oxaliplatin) in stage III dMMR disease, to the NICHE clinical trial series from the Netherlands, in which brief neoadjuvant nivolumab (Opdivo) plus 1 dose of ipilimumab (Yervoy) produced near-universal responses. Dr Kasi then detailed his own NEST trials, which replicated this short-course design using the Fc-enhanced CTLA-4 inhibitor botensilimab plus balstilimab, notably extending activity into the larger mismatch repair–proficient/microsatellite stable (MSS) population with sustained disease-free survival.Drs Park and Kasi explored mechanistic insights that have been seen with CRC drugs, including an "inside-out" serosal-to-mucosal response pattern, regulatory T cell depletion, and the rationale that an intact tumor and lymph nodes provide more antigens than the postsurgical setting. They also discussed circulating tumor DNA as an emerging surrogate end point, the implications of data from the phase 3 STELLAR-303 trial (NCT05425940) of an immunomodulatory TKI plus atezolizumab (Tecentriq) in patients with MSS disease, liver metastases as an immunosuppressive niche, and the alarming rise of early-onset CRC.

In today’s episode, we spoke with Nataliya Uboha, MD, PhD. Dr Uboha is an associate professor and researcher in the Department of Medicine at the University of Wisconsin School of Medicine in Madison.In our exclusive interview, Dr Uboha discussed the August 2026 FDA approval of zanidatamab (Ziihera)-based regimens for first-line HER2-positive locally advanced or metastatic gastric cancer, and unpacked data from the phase 3 HERIZON-GEA-01 trial (NCT05152147) that supported the regulatory decision. She also shed light on where zanidatamab fits in the gastric cancer treatment paradigm in combination with PD-1 inhibitors like tislelizumab (Tevimbra) and alongside other options like trastuzumab (Herceptin).

In today’s episode, Narjust Florez, MD, and Jonathan Wesley Riess, MD, MS, hosted a discussion about the distinction between HER2 overexpression and HER2 mutations in non–small cell lung cancer (NSCLC). Dr Florez is the associate medical director of the Cancer Care Access Program and a physician at Dana-Farber Cancer Institute, as well as an assistant professor of medicine and a faculty member at Harvard Medical School, both in Boston, Massachusetts. Dr Riess is the director of Thoracic Oncology and an associate professor of medicine in the Division of Hematology and Oncology at the University of California (UC) Davis Health Medical Center and the UC Davis Comprehensive Cancer Center in Sacramento.In our exclusive interview, Drs Florez and Riess clarified that HER2 mutations, commonly exon 20 insertions, are genomic drivers sensitive to TKIs, whereas HER2 overexpression is a protein finding identified by immunohistochemistry (IHC). They discussed the use of fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with HER2 IHC 3+ NSCLC, reviewed efficacy data from the DESTINY-Lung studies, and worked through a treatment sequencing case. Their conversation also addressed toxicity management, particularly aggressive nausea prophylaxis and vigilance for interstitial lung disease, and emphasized the importance of upfront HER2 testing to preserve tissue and save time.

In today’s episode, we spoke with Davide Melisi, MD, PhD. Dr Melisi is an associate professor of medical oncology at the University of Verona in Italy.In our exclusive interview, Dr Melisi discussed the investigational oral KRAS G12D inhibitor INCB161734, its mechanism of action, what early data have shown with the agent, and the aims of the ongoing phase 3 DAWN-303 trial (NCT07522073) evaluating it in patients with KRAS G12D–mutated metastatic pancreatic ductal adenocarcinoma. He also explored how the agent could be integrated into treatment sequencing alongside the August 2026 FDA approval of daraxonrasib (Rasonque) for the treatment of patients with metastatic disease.

In today’s episode, we spoke with Raji Shameem, MD, and Shubham Pant, MD, MBBS. Dr Shameem is a clinical assistant professor of medicine at the Orlando College of Osteopathic Medicine, an assistant professor of Medicine at the University of Central Florida, and a physician at Orlando Health. Dr Pant is a professor in the Department of Gastrointestinal Medical Oncology and the Department of Investigational Cancer Therapeutics, as well as the director of Clinical Research at The Sheikh Zayed Center For Pancreatic Cancer Research at The University of Texas MD Anderson Cancer Center in Houston.In our exclusive interview, Drs Shameem and Pant discussed the rapidly evolving pancreatic cancer treatment paradigm, going in-depth on topics like the role of liposomal irinotecan (Onivyde), the FDA approval of daraxonrasib (Rasonque) for patients with metastatic disease, and novel treatments that are in development. The 2 experts also covered which directions they see the pancreatic cancer field moving towards in the future.

Highlights from the PER® CME activity "SimulatED: Integrating Precision Pathways in HER2+ Gastroesophageal Adenocarcinoma — Testing, Treatment, and Supportive Care" — this podcast is not certified for credit. To participate in the full accredited activity and earn CME credit, use the link below.In this podcast, experts Geoffrey Y. Ku, MD, and Sunnie Kim, MD, discuss essential biomarker testing for advanced gastroesophageal adenocarcinoma, first-line treatment selection for HER2-positive metastatic disease in light of data from HERIZON-GEA-01 (NCT05152147), management of treatment-related diarrhea and other adverse events, and HER2 retesting at disease progression.Earn CME credit by completing the full accredited activity (available through August 31, 2027): https://www.gotoper.com/courses/simulated-integrating-precision-pathways-in-her2-gastroesophageal-adenocarcinoma-testing-treatment-and-supportive-careThis podcast, including the narration, was developed by PER® (Physicians’ Education Resource®, LLC) editorial staff from the full online CME activity developed with these faculty. The narration was voiced by a PER staff member or by an AI tool. The podcast contains no product advertising. The full activity is supported by an educational grant from Jazz Pharmaceuticals, Inc.This content is for educational purposes only and is not a substitute for the independent clinical judgment of a health care professional. Faculty may discuss investigational or off-label uses; consult prescribing information for any products discussed.