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 Vincent Chung, MD, about the development of atebimetinib (IMM-1-104) in metastatic pancreatic cancer. Dr Chung is a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope in Duarte, California.

In our exclusive interview, Dr Chung discussed MEK inhibition as a logical target in metastatic pancreatic cancer, the unique mechanism of action of atebimetinib that contributes to its improved tolerability relative to earlier-generation MEK inhibitors, key safety and efficacy findings from a phase 2a trial (NCT05585320) combining atebimetinib with modified gemcitabine/nab-paclitaxel (Abraxane) in patients with advanced or metastatic disease, and how the outcomes of the ongoing phase 3 MAPkeeper-301 trial may affect the treatment paradigm going forward.

In today’s episode, we spoke with Triparna Sen, PhD, and Jacob Sands, MD. Dr Sen is a professor of internal medicine and the director of the Lung Cancer Preclinical Therapeutics Platform at the Ohio State University Comprehensive Cancer Center—James in Columbus. Dr Sands is associate chief of the Lowe Center for Thoracic Oncology and the oncology medical director of the International Patient Center at Dana-Farber Cancer Institute, as well as an assistant professor at Harvard Medical School in Boston, Massachusetts.

In our exclusive interview, Drs Sen and Sands discussed findings from the phase 3 IMforte trial (NCT05091567), which showed that adding lurbinectedin (Zepzelca) to atezolizumab (Tecentriq) maintenance following carboplatin, etoposide, and atezolizumab induction improved outcomes in patients with extensive-stage small cell lung cancer (SCLC). Dr Sen noted that although the regimen’s safety profile was manageable, the combination does increase rate of hematologic toxicities, including anemia, neutropenia, and thrombocytopenia, so the key question is whether the added treatment burden is justified by longer disease control and survival. Dr Sands added that the neutropenia rates in IMforte were lower than in the earlier second-line lurbinectedin experience, likely because primary prophylaxis, such as granulocyte colony-stimulating factor, was permitted.

The experts also weighed in on a trial in progress presented at the 2026 World Conference on Lung Cancer evaluating lurbinectedin plus durvalumab (Imfinzi) as maintenance therapy. Dr Sen explained that a positive result could show that the strategy is reproducible with a different PD-L1 inhibitor and induction regimen but cautioned against assuming a class-wide effect or treating the 2 regimens as interchangeable. Dr Sands said he would not expect durvalumab to perform differently from atezolizumab in this context, and that the more pressing question is whether lurbinectedin belongs in maintenance at all, particularly as the IMforte curves have converged with longer follow-up. Both experts pointed to the phase 3 DeLLphi-305 trial (NCT06211036) of tarlatamab (Imdelltra) plus durvalumab vs durvalumab alone as first-line maintenance, which has reported positive OS and PFS results via press release, as the most significant development to watch in this space.

Turning to the relapsed setting, Drs Sen and Sands discussed the negative phase 3 LAGOON trial (NCT05153239), in which neither lurbinectedin monotherapy nor lurbinectedin plus irinotecan improved OS vs investigator’s choice of topotecan (Hycamtin) or irinotecan, leading to the withdrawal of lurbinectedin’s second-line indication. Dr Sands highlighted that the control arm median OS was unexpected given the median OS data that supported the original accelerated approval of the agent. Both experts emphasized that the LAGOON results should not be conflated with the maintenance data, and Dr Sands expressed hope that lurbinectedin remains a guideline-listed option in later lines, citing its convenient every-3-week dosing.

Finally, the experts looked ahead to emerging therapies. Dr Sands discussed B7-H3–directed antibody-drug conjugates (ADCs), including YL201 and ifinatamab deruxtecan. He also outlined practical toxicity management for ADCs, including cytopenias, nausea, fatigue, alopecia counseling, and the challenge of distinguishing drug-related interstitial lung disease from waxing and waning inflammatory findings common in SCLC. Dr Sen highlighted anticipated data at the 2026 ESMO Congress and stressed that treatment selection in SCLC maintenance will depend on magnitude of benefit, patient selection, toxicity, and center capabilities rather than a one-size-fits-all approach.

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).

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-practice
This 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 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.

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.