Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights From a Multicenter Real-World Study

Cholangiocarcinoma (CCA) is a rare cancer with limited therapeutic options and a poor prognosis. While first-line combination therapies have improved outcomes, second-line treatment remains challenging. Ivosidenib, an IDH1 inhibitor, has shown promise in treating IDH1 mutant CCA, but real-world data is limited. This study aims to evaluate ivosidenib's efficacy and safety in a large cohort of patients and compare it with second-line chemotherapy.

This observational, retrospective, multicenter study included patients with advanced IDH1 mutant CCA treated with ivosidenib at 11 European institutions from May 2021 to September 2024. The primary endpoint was progression-free survival (PFS); the main secondary objectives were overall survival (OS), disease control rate (DCR), overall response rate (ORR) and safety. As a pre-planned exploratory objective, mPFS and OS of second-line ivosidenib and FOLFOX/CAPOX were compared by means of inverse probability of treatment weights (IPTW)-adjusted analysis.

The study included 46 patients treated with Ivosidenib; 43.5% received ivosidenib as second line and 56.5% as ≥ third line. Median PFS and OS were 3.7 (95% CI, 2.2-36.5) and 11.5 months (95% CI, 9.5-36.5). DCR was 50.0%. Grade ≥ 3 adverse events occurred in 8.7% of patients. IPTW-adjusted mPFS was 6.9 months with ivosidenib and 2.1 months with FOLFOX/CAPOX (HR: 0.36, 95% CI, 0.20-0.64, p = 0.0005), while the mOS was 15.9 and 9.0 months with ivosidenib and FOLFOX/CAPOX, respectively (HR: 0.47, 95% CI, 0.23-0.96, p = 0.0405).

This study suggests that ivosidenib is a valid option for patients affected by metastatic IDH1 mutant CCA after at least one line of standard treatment.