The Phase 3 PEAK trial showed that adding the targeted drug bezuclastinib to sunitinib significantly improved outcomes for people with advanced gastrointestinal stromal tumors (GIST) who could not take imatinib or whose cancer had progressed on it. The combination cut the risk of cancer progression or death by half compared with sunitinib alone. Patients receiving the two-drug treatment had a median progression-free survival of 16.5 months, compared with 9.2 months for those taking sunitinib alone. The treatment also led to a higher response rate: 46% of patients responded to the combination versus 26% with sunitinib alone. Overall survival data are not yet mature.
The global randomized study tested bezuclastinib plus sunitinib against sunitinib alone in adults with advanced or metastatic GIST. The combination was generally well tolerated, and no unexpected safety issues were reported. The most common serious side effects included high blood pressure, low white blood cell counts, and increased liver enzymes. Liver-related side effects were usually temporary and manageable, requiring dose reductions in about 13% of patients and treatment discontinuation in only about 2%.
Experts consider these results highly meaningful and potentially practice-changing. The combination is expected to become the new standard second-line treatment for GIST.