JCO at ASCO 2026: Pemigatinib Phase 3 FIGHT-302 Trial in Cholangiocarcinoma

The FIGHT-302 trial evaluates the efficacy of the FGFR inhibitor pemigatinib compared to standard cisplatin and gemcitabine chemotherapy in patients with unresectable or metastatic cholangiocarcinoma harboring FGFR2 rearrangements. Despite early trial closure due to recruitment challenges and a shifting treatment landscape, results demonstrate a superior progression-free survival of 8.3 months for pemigatinib versus 6.8 months for chemotherapy, with a hazard ratio of 0.58. While the study reinforces the role of targeted therapy, clinical application requires balancing individual tumor characteristics and patient preferences against side effects like hyperphosphatemia and cutaneous toxicities. Future strategies must address resistance mechanisms, including kinase domain mutations and off-target pathway alterations, potentially through combination therapies or next-generation inhibitors. Dr. Eileen O'Reilly, JCO Associate Editor, emphasizes that while these findings support using targeted agents in the second-line setting, they also provide a viable option for frontline treatment.