Systematic review of randomized clinical trials of patients with IDH1 R132-mutant cholangiocarcinoma treated with ivosidenib.

Abstract

Objective: To evaluate the efficacy and safety of ivosidenib as a monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma harboring the IDH1R132 mutation, previously treated with at least one line of systemic therapy. Method: The evidence search was conducted in electronic databases Medline via PubMed, Embase, Cochrane and Lilacs, with a cutoff date of December 2024, to identify randomized clinical trials. Analyzed outcomes included progression-free survival (PFS), overall survival (OS), quality of life, and adverse events. Two investigators performed the search, study selection, data extraction, and assessed quality and risk of bias using the Cochrane RoB2 tool. The certainty of evidence was
analyzed with the support of the GRADE tool. Results: Two publications derived from the same pivotal randomized clinical trial, identified as ClarIDHy, were included. The median PFS was 2.7 months in patients treated with ivosidenib, compared to 1.4 months in those who received a placebo (HR = 0.37; 95%CI: 0.25 to 0.54). The six- and 12-month PFS rates were 32% and 22%, respectively. The final OS analysis indicated a benefit of ivosidenib compared to placebo. Overall, the safety profile of ivosidenib was favorable, with nausea, diarrhea, and fatigue being the most commonly reported adverse events in both groups. Conclusion: In patients with locally advanced or metastatic cholangiocarcinoma harboring the IDH1 mutation, ivosidenib
emerges as a viable therapeutic option; however, this conclusion should be interpreted with caution, as it is primarily based on two publications derived from a single pivotal clinical trial, which limits the robustness of the available evidence.