Background: Futibatinib, an irreversible FGFR1–4 inhibitor, is being investigated for the treatment of advanced intrahepatic cholangiocarcinoma (iCC) with FGFR2 fusions/rearrangements. We conducted an indirect treatment comparison to evaluate efficacy outcomes with futibatinib for advanced iCC patients from the FOENIX-CCA2 trial (NCT02052778) relative to published data for chemotherapy and FGFR inhibitors. Methods: A systematic literature review was conducted to identify clinical trials for FGFR inhibitors published 01/2015-02/2021, with additional targeted searches for chemotherapy data. A simulated treatment comparison was conducted using individual-level patient data from FOENIX-CCA2 and published aggregate data from comparator trials, applying regression models to adjust for between-trial differences in baseline characteristics. Population-adjusted Cox regression models were used for base case time-to-event outcomes (progression-free survival [PFS], overall survival [OS], duration of response [DOR]) and binomial-logistic regressions for binary outcomes (objective response rate [ORR]). Results: Two studies of FGFR inhibitors among previously treated patients with FGFR2 fusions/rearrangements were identified with sufficient data for analysis: FOENIX-CCA2 (n=103) and FIGHT-202 (n=107, pemigatinib). Two studies were identified for chemotherapy in this setting (an analysis of prior systemic therapy in the FIGHT-202 cohort [n=53] and a natural history study using a clinicogenomic database [n=71]). Comparisons of futibatinib with chemotherapy showed significantly lower risk of progression or death with futibatinib (table). Comparisons of futibatinib with pemigatinib showed similar outcomes between treatments (table), however, there was a numerical advantage for futibatinib in all efficacy parameters. Conclusions: Data suggest that futibatinib provides longer survival vs chemotherapy among previously treated advanced iCC patients with FGFR2 fusions/rearrangements. No statistically significant differences were observed in efficacy outcomes between futibatinib and pemigatinib, although numerical trends favored futibatinib. Molecular detail such as improved activity against co-mutated tumours and resistance mutations may explain such trends.

*p≤0.01. ^aValues <1 favor futibatinib; ^bValues >1 favor futibatinib. HR, hazard ratio; CI, confidence interval