This phase 3 study randomised 185 patients with advanced cholangiocarcinoma and IDH1 mutations to ivosidenib or matched placebo. Patients could crossover from placebo to ivosidenib when their disease progressed. Median progression-free survival was 2.7 months for patients treated with ivosidenib compared to 1.4 months with placebo (hazard ratio [HR] 0.37; 95% confidence interval [CI]: 0.25, 0.54, p<0.001). The median progression-free survival rate at six months was 32.0% with ivosidenib, while no patients randomised to placebo were free from progression at this timepoint. Median overall survival was 10.8 months for ivosidenib and 9.7 months for placebo (HR 0.69, one-sided p=0.06). Adjusting the overall survival results to take account of 57% of placebo patients crossing over to ivosidenib gave an adjusted overall survival of 6 months for placebo, which was significantly shorter than with ivosidenib (HR 0.46, p=0.0008). Finally, Grade 3 or higher adverse events reported in 46% of patients on the targeted agent and 36% of those on placebo, and there were no treatment-related deaths. his is the first pivotal study demonstrating the clinical benefit of targeting mIDH1 in pts with advanced mIDH1 cholangiocarcinoma.
(G.K. Abou-Alfa et al- Annals of Oncology, September 2019)