Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial

作者：Xuefeng Fang, Ning Zhu, Chenhan Zhong, Liuhong Wang, Jun Li, Shanshan Weng, Hanguang Hu, Caixia Dong, Dan Li, Yongmao Song, Dong-Hui Xu, Jianwei Wang, Lifeng Sun, Jian Wang, Zhanhuai Wang, Hongfeng Cao, Xiujun Liao, Ningjuan Yu, Qian Xiao, Mi Mi, Suzhan Zhang, Kefeng Ding, Ying Shu Yuan · 发表于：EClinicalMedicine · 年份：2023 · DOI：10.1016/j.eclinm.2023.102123 · 被引用次数：34 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Genomics and Diagnostics、Genetic factors in colorectal cancer

Background: Microsatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) patients are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and anti-angiogenesis therapy have been reported to potentially promote immunotherapy response. This study aims to assess the preliminary anti-tumor activity and safety of sintilimab plus bevacizumab, oxaliplatin and capecitabine as a treatment option for patients with RAS-mutant MSS mCRC. Methods: , day 1-14) in each 21-day cycle. The primary endpoints included objective response rate (ORR) and adverse events. Biomarker analysis was performed to identify potential predictors of good response to treatment. This study is registered with ClinicalTrials.gov, number NCT04194359. Findings: Between April 2021 and December 2021, 25 patients were enrolled. Two (8%) patients showed complete response (CR), 19 (76%) had partial response (PR) and 4 (16%) presented with stable disease. ORR reached 84% (95% CI, 63.9-95.5) and the disease control rate was 100% (95% CI, 86.3-100). The median progression-free survival (PFS) was 18.2 months for the full analysis set. The most common treatment-related adverse events (TRAEs) in all grades were anemia (21/25, 84%), neutropenia (20/25, 80%), and hand-foot syndrome (14/25, 56%). The most frequent grade 3 or 4 TRAEs were neutropenia (3/25, 12%) and increased alanine transaminase (2/25, 8%). No grade 5 adverse events occurred. In the explor...