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

• DOI: 10.1016/j.jtho.2021.07.015
• Publication Date: 2021-08-03T16:10:50Z
• Authors: 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 Lu; Hui Zhou; Shuyan Wang; Luyao Sun; Oscar Puig; Christoph Mancao; Bo Peng; Wenfeng Fang; Wei Xu; Li Zhang
• Keywords: Pemetrexed; Progression-free survival

IntroductionSintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with alone in nonsquamous NSCLC the ORIENT-11 study. Updated overall (OS) and PFS data corresponding biomarker analyses are reported here.MethodsIn this study, a total of 397 patients previously untreated, locally advanced or metastatic were assigned to sintilimab combination treatment (combo) group placebo group. The stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing PD-L1 immunohistochemistry correlated clinical outcome identify predictive biomarkers.ResultsAs January 2021, median follow-up 22.9 months, OS was improved combo (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45–0.79, p 0.0003). High medium immune cell infiltration strongly associated group, contrast absent low infiltration, which suggests that could not prime "immune deserts" obtain benefit death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway (HR 0.32, CI: 0.19–0.54, < 0.0001) 0.36, 0.20–0.64, 0.0005) Importantly, but MHC still treatment. contrast, I antigen less relevant setting.ConclusionsThe addition resulted longer NSCLC. Expression benefiting most combination.