Mark Agulnik, MD

The panel discusses exciting future developments including expanded interest in first-line combination strategies and targeting multiple resistance mechanisms simultaneously. Companies are increasingly developing agents specifically for GIST rather than repurposing drugs designed for other malignancies.

Dr. Schulte outlines toxicity management strategies across the GIST treatment sequence, emphasizing proactive patient education and monitoring. Imatinib's 25-year track record provides community comfort with characteristic side effects including edema, myalgias, and gastrointestinal irritation, managed with full stomach dosing and symptomatic measures.

Dr. Pollack emphasizes tissue-based next-generation sequencing as the gold standard for initial diagnosis and primary driver mutation identification. This testing remains absolutely essential at diagnosis to distinguish KIT-mutant from PDGFRA-mutant GIST and identify rare entities like SDH-deficient or NTRK-fusion tumors requiring different treatment approaches.

Dr. Somaiah addresses the critical question of treatment sequencing after combination second-line therapy, acknowledging that all currently approved agents were studied as sequential monotherapies without prospective data on their performance following combination treatment. This represents uncharted territory requiring clinical experience and real-world data collection.

Dr. Schulte addresses the critical question of combination tolerability compared to sunitinib monotherapy, noting that community oncologists' primary concern involves adding a second agent to an already challenging treatment regimen. The PEAK Part 1 safety data provided reassuring evidence that combination therapy doesn't substantially increase toxicity burden.

Dr. Pollack addresses clinicians' desire for mutation-specific response data before adopting combination therapy, emphasizing the transformative insights from the INTRIGUE trial's ctDNA analysis. The INTRIGUE study demonstrated dramatic differences in patients with KIT exon 11 mutations based on secondary resistance patterns: those with exon 13/14 secondary mutations achieved over 12 months progression-free survival with sunitinib versus only months with ripretinib, while the reverse pattern held for exon 17/18 secondary mutations.

Dr. Agulnik outlines bezuclastinib's regulatory trajectory, noting Breakthrough Therapy Designation granted in March 2026 based on PEAK topline results. This designation indicates the drug addresses unmet medical need with substantial improvement over available therapy. The New Drug Application was accepted under Real-Time Oncology Review with submission completed in April 2026.

Dr. Heinrich explains the scientific foundation for combining bezuclastinib with sunitinib, addressing the fundamental problem of polyclonal resistance emerging after imatinib progression.

Dr. Schulte identifies significant knowledge gaps among community oncologists managing GIST, acknowledging that even experienced community practitioners may encounter only 2 to 3 patients annually. This limited exposure creates challenges in maintaining expertise with nuanced treatment decisions and sequencing strategies.

Dr. Pollack characterizes ripretinib as an outstanding fourth-line agent that filled a critical unmet need in post-third-TKI progression settings. Before ripretinib's availability, patients lacked effective treatment options after exhausting the first three lines of therapy.

Dr. Agulnik analyzes the INTRIGUE trial's landmark contributions to GIST management, representing the first head-to-head Phase 3 comparison rather than placebo-controlled study.

Dr. Somaiah outlines the current FDA-approved sequence for advanced KIT-mutant GIST, emphasizing that community oncologists may encounter only handful of patients annually. First-line therapy uses imatinib 400mg daily, escalating to 400mg twice daily for KIT exon 9 mutations based on superior activity data.

Dr. Jason Sicklick from UC San Diego introduces this OncLive Peer Exchange program addressing the evolving post-third-line GIST landscape, joined by sarcoma experts Dr. Mark Agulnik, Dr. Neeta Somaiah, Dr. Michael Heinrich, Dr. Seth Pollack, and Dr. Brian Schulte. The discussion focuses on the first positive Phase 3 second-line trial in over two decades currently under FDA review.

In this episode, experts highlight the key takeaways from the Stand Up to Cancer SARC 032 study and its clinical implications.

In this episode, experts discuss the landmark SARC 032 study, highlighting the importance of multidisciplinary collaboration.

In this episode, experts discuss the impact of neoadjuvant radiation and immunotherapy on surgical planning in patients with soft tissue sarcomas.

In this episode, experts shed light on the surgical approach to soft tissue sarcomas.

In this episode, experts discuss the potential of radiation therapy to enhance immune response in soft tissue sarcomas.

In this episode, experts discuss the rationale behind the combined treatment in the Stand Up to Cancer SARC 032 trial.

In this episode, experts discuss the latest advancements in the multimodal treatment of undifferentiated pleomorphic sarcoma of the extremities.

Mark Agulnik, MD, discusses the evolving management of heterogeneous disease types in gastrointestinal stromal tumors.

Dr Agulnik spotlights key updates from across the GIST landscape ahead of GIST Awareness Day on July 13.

A panel of oncology experts provides insights into the future outlook for desmoid tumor treatment, discussing anticipated developments in the field.

Expert oncologists discuss the recent approval of nirogacestat for the treatment of desmoid tumors and explore its impact on clinical practice and the future treatment landscape.

A panel of oncology experts discuss the impact of nirogacestat on pain symptoms and quality of life indicators for individuals with desmoid tumors, as well as the possible effects on ovarian function.

Jonathan Trent, MD, PhD, discusses the rationale and design of the DeFi study, instrumental in the FDA approval of nirogacestat, and explores key efficacy and safety findings from this research.

Mark Agulnik, MD, examines the mechanism of action of nirogacestat, emphasizing the impact of ϒ-secretase inhibition on NOTCH pathway signaling.

A panel of oncology experts provides insights into the management of desmoid tumors in women, focusing on special considerations for pregnancy and contraception.

Jonathan Trent, MD, PhD, discusses the role of approaches using low-dose and conventional chemotherapy, emphasizing key consideration factors for patient selection.

Mark Agulnik, MD, gives a summary of approaches to systemic therapy in the management of desmoid tumors, highlighting the diminishing role of chemotherapy and the shift towards targeted therapies.