Background & Aims: 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. Methods: 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. Results: 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). Conclusion: 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.
Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights From a Multicenter Real-World Study / Niger, M.; Rimini, M.; Castet, F.; Melzer, A.; Rizzato, M. D.; Pressiani, T.; Lavacchi, D.; Aprile, G.; Angela, T.; Saladino, T.; Silvia, N.; Cito, P.; Pastorino, A.; Teran-Brage, E.; Sciortino, C.; Camera, S.; Pircher, C.; Persano, M.; Mazzaferro, V.; Foti, S.; Vega, K. S.; Ettrich, T. J.; Antonuzzo, L.; Rimassa, L.; Lonardi, S.; Perkhofer, L.; Macarulla, T.; Pietrantonio, F.; Casadei-Gardini, A.. - In: LIVER INTERNATIONAL. - ISSN 1478-3223. - 45:9(2025). [10.1111/liv.70295]
Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights From a Multicenter Real-World Study
Rimini M.;Casadei-Gardini A.
2025-01-01
Abstract
Background & Aims: 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. Methods: 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. Results: 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). Conclusion: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
