Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study

作者：Yunpeng Yang, Jiya Sun, Zhehai Wang, Jian Fang, Qitao Yu, Baohui Han, Shundong Cang, Gongyan Chen, Xiaodong Mei, Zhixiong Yang, Rui Ma, Minghong Bi, Xiubao Ren, Jianying Zhou, Baolan Li, Yong Song, Jifeng Feng, Juan Li, Zhiyong He, Rui Zhou, Weimin Li, You Lü, Hui Zhou, Shuyan Wang, Luyao Sun, Óscar Puig, Christoph Mancao, Bo Peng, Wenfeng Fang, Wei Xu, Li Zhang · 发表于：Journal of Thoracic Oncology · 年份：2021 · DOI：10.1016/j.jtho.2021.07.015 · 被引用次数：154 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Colorectal and Anal Carcinomas

INTRODUCTION: Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here. METHODS: In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers. RESULTS: As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (...