Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial

作者：Teresa Macarulla, Zhenggang Ren, Hong Jae Chon, Joon Oh Park, Jin Won Kim, Tiziana Pressiani, Daneng Li, Lyudmila Zhukova, Andrew X. Zhu, Ming‐Huang Chen, Stephen P. Hack, Stephanie Wu, Bo Liu, Xiangnan Guan, Shan Lu, Yulei Wang, Anthony B. El-Khoueiry · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.24.00337 · 被引用次数：37 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Pancreatic and Hepatic Oncology Research、Gallbladder and Bile Duct Disorders

PURPOSE Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti–vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition. PATIENTS AND METHODS This randomized, double-blind, proof-of-concept phase II study enrolled patients (n = 162) with previously untreated advanced BTC (IMbrave151; ClinicalTrials.gov identifier: NCT04677504 ). Patients were randomly assigned 1:1 to receive cycles of atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo once every 3 weeks until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg/m 2 ) plus gemcitabine (1,000 mg/m 2 ; cisplatin plus gemcitabine [CisGem]) on days 1 and 8 once every 3 weeks for up to eight cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary end point was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n = 95) and mutation profiling (n = 102) on baseline tumor samples. RESULTS Between February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo arm (stratified hazard ratio [HR], 0.67 [95% CI, 0.46 to 0.95]). Median overall survival (OS) was 14.9 and 14.6 months in...