Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase 3 FIGHT-302 Trial.

Abstract

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. FIGHT-302 is a phase 3, randomized, global trial evaluating pemigatinib as first-line therapy (NCT03656536). Adults with advanced cholangiocarcinoma with <i>FGFR2</i> 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. 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 <i>P</i>=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. This was the largest, first-line, randomized, phase 3 trial of a targeted therapy for advanced <i>FGFR2-</i>rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.