First-Line Pemigatinib in Fgfr2-Rearranged Cholangiocarcinoma

Key Takeaways

• First-line pemigatinib was associated with longer progression-free survival than gemcitabine-cisplatin in this biomarker-defined population.
• Response outcomes favored pemigatinib, with higher objective response and longer response duration than chemotherapy.
• Overall survival was similar between groups, chemotherapy progression allowed crossover to pemigatinib, and safety matched the known pemigatinib profile.

First-line pemigatinib prolonged progression-free survival compared with gemcitabine-cisplatin in adults with FGFR2-rearranged unresectable or metastatic cholangiocarcinoma in the Journal of Clinical Oncology report on FIGHT-302. Median progression-free survival was 8.3 months with pemigatinib and 6.8 months with chemotherapy, with a hazard ratio of 0.58 (95% CI, 0.39-0.87; nominal P=0.0078). FIGHT-302 was a phase 3 randomized global trial in a biomarker-selected population receiving initial systemic therapy for advanced disease. The trial enrolled patients with FGFR2 rearrangement rather than an unselected biliary tract cancer cohort. It adds randomized first-line data in FGFR2-rearranged cholangiocarcinoma.

The phase 3 global trial enrolled adults with advanced cholangiocarcinoma harboring FGFR2 rearrangement and randomly assigned 83 patients to pemigatinib and 84 to gemcitabine-cisplatin. Pemigatinib was given at 13.5 mg once daily, while chemotherapy comprised gemcitabine 1000 mg/m2 plus cisplatin 25 mg/m2 on days 1 and 8 every 3 weeks. The primary endpoint was progression-free survival, and chemotherapy could continue for up to 8 cycles, with crossover to pemigatinib allowed after progression. Randomization was stratified by prior receipt of chemotherapy, geographic region, and baseline tumor burden at enrollment. Researchers prescreened 4563 patients, screened 196, and randomized 167 before early closure after a change in standard of care.

Objective response rate was 47% with pemigatinib and 15% with chemotherapy, while median duration of response was 14.2 months and 6.3 months, respectively. Median overall survival was 24.4 months with pemigatinib and 25.0 months with chemotherapy, indicating similar survival between the treatment groups at the reported analysis. Response outcomes separated the groups more clearly than overall survival during the reported analysis period. Pemigatinib was associated with higher response rates and longer response duration alongside the progression-free survival advantage. Overall survival remained comparable across the randomized groups during reported follow-up.

Among 42 patients who crossed over after chemotherapy progression, median progression-free survival with second-line pemigatinib was 8.1 months. These crossover results added post-progression information within the trial design but did not alter the primary randomized comparison. Adverse events were consistent with the known pemigatinib profile, and investigators reported no new safety findings. Investigators described FIGHT-302 as the largest first-line randomized phase 3 targeted-therapy trial in advanced FGFR2-rearranged cholangiocarcinoma.