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.
Learn how clinicians address fertility risks from newer cancer therapies, discuss ovarian toxicity, pregnancy avoidance, and when to refer for preservation.
Learn how clinicians proactively manage toxicities from targeted systemic cancer therapies, using early education, monitoring, and dose adjustments to maintain adherence.
Desmoid tumor care shifts from surgery to systemic options like gamma secretase inhibitors; experts weigh chemo, TKIs, and selective cryoablation or radiation.
Experts provide practical recommendations for community oncologists managing gastrointestinal stromal tumors (GIST), emphasizing optimized molecular testing and treatment sequencing decisions, and offering guidance on when and how to refer patients to specialized centers.
Experts discuss the preliminary results of the PEAK study on the combination of bezuclastinib and sunitinib in second-line gastrointestinal stromal tumors (GIST), its potential to address heterogeneous resistance mutations, and how mutation-specific, biomarker-driven approaches in ongoing trials like INSIGHT may shift the treatment paradigm compared with traditional line-of-therapy strategies.
Experts discuss how they approach managing adverse events with tyrosine kinase inhibitors (TKIs) like ripretinib, sunitinib, and regorafenib, highlighting notable differences in their safety profiles and how these differences influence treatment decisions.
Experts discuss the key insights from the follow-up exploratory analysis of the INTRIGUE trial investigating circulating DNA (ctDNA) biomarkers and how mutation-specific findings may influence molecular testing before selecting a second-line agent, with practical implications for implementing a more personalized approach in clinical practice.
Experts discuss the key findings from the INTRIGUE trial comparing ripretinib to sunitinib in the second-line setting, focusing on efficacy endpoints like progression-free survival (PFS) and PFS on next line of therapy, and interpret the patient-reported outcome (PRO) and tolerability data reported in the study.
Experts discuss the key efficacy and safety findings from the INVICTUS trial that established ripretinib in the fourth-line setting, and how the inclusion of ripretinib has influenced their approach to managing patients with heavily pretreated gastrointestinal stromal tumors (GIST).
Experts discuss key factors influencing decision-making when patients with advanced gastrointestinal stromal tumors (GIST) progress on imatinib, reviewing standard second-line options, considerations for increasing imatinib dosing vs switching to a different tyrosine kinase inhibitor (TKI), and clinical or radiographic patterns that guide therapy changes or dose escalation at progression.
Experts discuss the tools available to monitor tumor heterogeneity and detect resistance, examining the reliability of current testing methods, differences in molecular testing for newly diagnosed metastatic patients vs those who have progressed, the role of liquid biopsy compared to traditional tissue biopsy, and how these test results inform risk assessment and clinical decision-making.
Experts discuss the biological mechanisms of resistance in gastrointestinal stromal tumors (GIST), differentiating between primary and secondary resistance, and explore how tumor heterogeneity evolves throughout treatment, with implications for long-term management and treatment strategies.
Experts discuss optimizing TKI selection and sequencing strategies for advanced gastrointestinal stromal tumors (GIST) beyond first-line therapy, focusing on the latest clinical data, molecular characterization, and insights from recent trials to guide treatment decisions.
