PEAK Trial Results With Bezuclastinib Plus Sunitinib in GIST

This segment covers the panelists' review of the pivotal PEAK trial, which randomly assigned patients with KIT-mutant gastrointestinal stromal tumor (GIST) to bezuclastinib plus sunitinib or sunitinib alone after imatinib, using progression-free survival by blinded independent central review as the primary end point and permitting crossover at progression. The panelists discuss a substantial improvement in progression-free survival with the combination, reaching double digits in a setting where that has not been seen, along with a markedly higher overall response rate. They then talk through tolerability, describing more frequent transaminase elevation with bezuclastinib that was generally managed with dose reduction, while fatigue, diarrhea, and neutropenia were comparable between arms and hand-foot syndrome and thrombocytopenia actually favored the combination. They also discuss the monitoring schedule, including frequent early laboratory checks, and the possibility that pharmacokinetic interaction improved sunitinib tolerability.