Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial

作者：Shun Lü, Jie Wang, Yan Yu, Xinmin Yu, Yanping Hu, Xinghao Ai, Zhiyong Ma, Xingya Li, Wu Zhuang, Yunpeng Liu, Weidong Li, Jiuwei Cui, Dong Wang, Wangjun Liao, Jianying Zhou, Zhehai Wang, Yuping Sun, Xiusong Qiu, Jie Gao, Yuanyuan Bao, Liang Liang, Mengzhao Wang · 发表于：Journal of Thoracic Oncology · 年份：2021 · DOI：10.1016/j.jtho.2021.05.005 · 被引用次数：284 · 研究领域：Cancer Immunotherapy and Biomarkers、Monoclonal and Polyclonal Antibodies Research、Esophageal Cancer Research and Treatment

INTRODUCTION: Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC). METHODS: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points. RESULTS: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most co...