This is the report of a phase 3 study assessing efficacy and safety of ivosidenib, a small-molecule targeted inhibitor of mutated IDH1, in patients with previously treated IDH1-mutant advanced cholangiocarcinoma. 185 patients were randomized 2:1 to receive ivosidenib or placebo. Median progression-free survival was 2.7 months for ivosidenib vs 1.4 months for placebo (HR 0.37; 95%CI 0.25-0.54; P<0.0001). Median overall survival (OS) was 10.8 months for ivosidenib vs 9.7 months for placebo (HR 0.69; 95%CI 0.44-1.1; P=0.06). However, the trial allowed the crossover and 57% of the patients randomized to placebo received ivosidenib at disease progression. According to the pre-planned rank-preserving structural failure time (RPSFT) method, adjusted median OS for placebo was 6.0 months, resulting in a significant improvement for ivosidenib vs placebo (HR 0.46; 95%CI 0.28-0.75; P=0.0008). Most common grade ≥3 adverse event (AE) in both treatment groups was ascites (7%). Serious AEs were reported in 36 (30%) and 13 (22%) patients for ivosidenib and placebo, respectively.

(Abou-Alfa GK et al. – Lancet Oncol, 13 May 2020)

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