OBJECTIVES: Futibatinib, an irreversible FGFR1-4 inhibitor, demonstrated efficacy among previously treated patients with intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements in the FOENIX-CCA2 (NCT02052778) pivotal phase 2 trial. An indirect treatment comparison (ITC) was conducted to evaluate efficacy outcomes with futibatinib in FOENIX-CCA2 relative to published data for chemotherapy and the FGFR inhibitor pemigatinib. There are conflicting simulation studies on the most suitable methods for ITC in health technology assessment, in particular matching-adjusted indirect comparison (MAIC) versus simulated treatment comparison (STC). Ambiguity regarding the best approach is greater in the unanchored setting, where there is no common comparator. In this ITC we utilised unanchored MAIC to avoid making parametric assumptions required by STC.

METHODS: A systematic literature review identified clinical trials for FGFR inhibitors published 01/2015–02/2021, with additional targeted searches for chemotherapy data. Unanchored MAIC was conducted using individual-level patient data for futibatinib from FOENIX-CCA2 and published aggregate data from comparator trials, using potential confounding baseline characteristics for matching.

RESULTS: Two FGFR inhibitor studies FOENIX-CCA2 (futibatinib) and FIGHT-202 (pemigatinib) and two chemotherapy studies were included, with no common comparator. For futibatinib versus chemotherapy (effective sample size [ESS]=48.5), hazard ratios (HRs; 95% CI) were 0.48 (0.30-0.76; p=0.002) for progression-free survival (PFS) and 0.48 (0.31-0.74; p=0.001) for overall survival (OS). Futibatinib versus pemigatinib (ESS=91.3) showed similar treatment effects, although HRs numerically favoured futibatinib: 0.83 (0.58-1.17; p=0.287) for PFS, 0.88 (0.58-1.34; p=0.564) for OS, 0.80 (0.42-1.50; p=0.489) for duration of response; odds ratio for objective response was 1.28 (0.72-2.25; p=0.399), reflecting a trend towards higher response rates with futibatinib.

CONCLUSIONS: There was evidence that futibatinib improves survival outcomes versus chemotherapy among previously treated iCCA patients with FGFR2 fusions/rearrangements. While efficacy outcomes were similar for futibatinib versus pemigatinib, numerical trends favoured futibatinib. Future work in this setting will further explore both MAIC and STC approaches.