Background
Phase 3, randomized, global, open-label trial; first-line therapy for unresectable/metastatic cholangiocarcinoma with FGFR2 fusion/rearrangement; N=167 randomized (4563 prescreened, 196 screened); closed early due to a change in first-line standard of care.
Results
Interventions and follow up: Arm A: Pemigatinib 13.5 mg PO once daily (2 wk on / 1 wk off) (n=83)
Arm B: Gemcitabine 1000 mg/m² + cisplatin 25 mg/m² IV days 1 & 8 q3wk, ≤8 cycles (n=84); crossover to pemigatinib allowed on progression
Primary endpoint: PFS
mFollow up: NR
Results: PFS: 8.3 vs 6.8 mo; HR 0.58 (95% CI 0.39–0.87); nominal P=.0078
ORR: 47% vs 15%
DOR (median): 14.2 vs 6.3 mo
OS (median): 24.4 vs 25.0 mo (NS; crossover allowed)
Crossover (2nd-line pemigatinib, n=42): median PFS 8.1 mo
Arm B: Gemcitabine 1000 mg/m² + cisplatin 25 mg/m² IV days 1 & 8 q3wk, ≤8 cycles (n=84); crossover to pemigatinib allowed on progression
Primary endpoint: PFS
mFollow up: NR
Results: PFS: 8.3 vs 6.8 mo; HR 0.58 (95% CI 0.39–0.87); nominal P=.0078
ORR: 47% vs 15%
DOR (median): 14.2 vs 6.3 mo
OS (median): 24.4 vs 25.0 mo (NS; crossover allowed)
Crossover (2nd-line pemigatinib, n=42): median PFS 8.1 mo
Adverse events
Overall: consistent with the known pemigatinib profile; no new safety signals
Class effects: hyperphosphataemia, stomatitis, nail/skin changes, serous retinal detachment
Class effects: hyperphosphataemia, stomatitis, nail/skin changes, serous retinal detachment
Conclusions
First-line pemigatinib significantly prolonged PFS and roughly tripled ORR vs gemcitabine/cisplatin in FGFR2-rearranged cholangiocarcinoma — the largest randomized first-line FGFR-inhibitor dataset — but OS was not improved (confounded by crossover) and the study closed early.
Key Limitations
Stopped early (N=167, well below planned enrollment) and thus underpowered; rarity of FGFR2 rearrangement (<4% prescreen positivity); open-label; OS uninterpretable due to crossover; comparator was gemcitabine/cisplatin alone, no longer the first-line standard; PFS P-value nominal (not formally controlled).
Clinical Context
Pemigatinib (Pemazyre) holds FDA accelerated (2020) and EMA approval for FGFR2-rearranged cholangiocarcinoma after ≥1 prior line, based on phase 2 FIGHT-202. First-line standard is now gemcitabine/cisplatin + durvalumab (TOPAZ-1) or + pembrolizumab (KEYNOTE-966). FIGHT-302 supports pemigatinib as a first-line option, but with no OS gain and early closure, FGFR2 inhibitors remain principally a later-line standard per NCCN/ESMO; upfront molecular profiling is essential.