Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11)

作者：Yunpeng Yang, Zhehai Wang, Jian Hong 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, Yingyi Wang, Lijun Wang, Nong Yang, Yan Zhang, Zhuang Yu, Yanqiu Zhao, Conghua Xie, Ying Cheng, Hui Zhou, Shuyan Wang, Donglei Zhu, Wen Zhang, Li Zhang · 发表于：Journal of Thoracic Oncology · 年份：2020 · DOI：10.1016/j.jtho.2020.07.014 · 被引用次数：403 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Treatments and Mutations、Lymphoma Diagnosis and Treatment

INTRODUCTION: Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539). METHODS: A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee. RESULTS: As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combin...