Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase 3 FIGHT-302 Trial
Mené sur 167 patients atteints d'un cholangiocarcinome avec réarrangements du gène FGFR2 et non résécable ou métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du pémigatinib
Purpose: Cholangiocarcinoma is a rare cancer associated with poor prognosis. Pemigatinib was the first FGFR1-3 inhibitor approved for second-line therapy and beyond, based on the phase 2 FIGHT-202 trial. Here, we assess efficacy and safety of first-line pemigatinib.
Patients and Methods: FIGHT-302 is a phase 3, randomized, global trial evaluating pemigatinib as first-line therapy (NCT03656536). Adults with advanced cholangiocarcinoma with FGFR2 rearrangement were randomized 1:1 to receive pemigatinib (13.5 mg once daily) or chemotherapy (1000 mg/m2 gemcitabine plus 25 mg/m2 cisplatin on days 1 and 8 of every 3-week cycle for ≤8 cycles) and were stratified by prior receipt of chemotherapy, geographic region, and tumor burden. Pemigatinib crossover was allowed for patients progressing on chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary efficacy, safety, and exploratory endpoints were also analyzed.
Results: Overall, 4563 patients were prescreened, 196 were screened, and 167 randomized to receive pemigatinib (n=83) or chemotherapy (n=84) before early closure of the study due to a change in standard of care. Median PFS was 8.3 months in the pemigatinib group versus 6.8 months in the chemotherapy group (hazard ratio [95% CI], 0.58 [0.39-0.87]; nominal P=0.0078); objective response rate was 47% versus 15%, and median duration of response was 14.2 versus 6.3 months. Median OS was similar (24.4 versus 25.0 months, respectively). In the crossover group (n=42, second-line pemigatinib), median PFS was 8.1 months. Safety was consistent with the known profile of pemigatinib.
Conclusion: This was the largest, first-line, randomized, phase 3 trial of a targeted therapy for advanced FGFR2-rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.
Journal of Clinical Oncology , résumé, 2026