Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation

作者：Andrew X. Zhu, Teresa Macarulla, Milind Javle, Robin Kate Kelley, Sam Joseph Lubner, Jorge Adeva, James M. Cleary, Daniel V.T. Catenacci, Mitesh J. Borad, John Bridgewater, William Proctor Harris, Adrian Murphy, Do‐Youn Oh, Jonathan Whisenant, Maeve A. Lowery, Lipika Goyal, Rachna T. Shroff, Anthony B. El-Khoueiry, Christina X. Chamberlain, Elia Aguado-Fraile, Sung Choe, Bin Wu, Hua Liu, Camelia Gliser, Shuchi S. Pandya, Juan W. Valle, Ghassan K. Abou‐Alfa · 发表于：JAMA Oncology · 年份：2021 · DOI：10.1001/jamaoncol.2021.3836 · 被引用次数：491 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Gastric Cancer Management and Outcomes、Fibroblast Growth Factor Research

IMPORTANCE: Isocitrate dehydrogenase 1 (IDH1) variations occur in up to approximately 20% of patients with intrahepatic cholangiocarcinoma. In the ClarIDHy trial, progression-free survival as determined by central review was significantly improved with ivosidenib vs placebo. OBJECTIVE: To report the final overall survival (OS) results from the ClarIDHy trial, which aimed to demonstrate the efficacy of ivosidenib (AG-120)-a first-in-class, oral, small-molecule inhibitor of mutant IDH1-vs placebo for patients with unresectable or metastatic cholangiocarcinoma with IDH1 mutation. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized, double-blind, placebo-controlled, clinical phase 3 trial was conducted from February 20, 2017, to May 31, 2020, at 49 hospitals across 6 countries among patients aged 18 years or older with cholangiocarcinoma with IDH1 mutation whose disease progressed with prior therapy. INTERVENTIONS: Patients were randomized 2:1 to receive ivosidenib, 500 mg, once daily or matched placebo. Crossover from placebo to ivosidenib was permitted if patients had disease progression as determined by radiographic findings. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival as determined by blinded independent radiology center (reported previously). Overall survival was a key secondary end point. The primary analysis of OS followed the intent-to-treat principle. Other secondary end points included objective response rate, safety and t...