Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study

• DOI: 10.1136/jitc-2019-000381
• Publication Date: 2020-06-30T19:52:30Z
• Authors: Xue Bai; De-Hua Wu; Si-Cong Ma; Jian Wang; Xin-Ran Tang; Shuai Kang; Qiang John Fu; Chuan-Hui Cao; He-San Luo; Yu-Han Chen; Hong-Bo Zhu; Hong-Hong Yan; Yi-Long Wu; Zhong-Yi Dong
• Keywords: STK11

Background Genetic variations of some driver genes in non-small cell lung cancer (NSCLC) had shown potential impact on immune microenvironment and associated with response or resistance to programmed death protein 1 (PD-1) blockade immunotherapy. We therefore undertook an exploratory analysis develop a genomic mutation signature (GMS) predict the anti-PD-(L)1 therapy. Methods In this multicohort analysis, 316 patients non-squamous NSCLC treated from three independent cohorts were included our study. Tumor samples molecularly profiled by MSK-IMPACT whole exome sequencing. developed risk model named GMS based MSK training cohort (n=123). The predictive was first validated separate internal (n=82) then external containing 111 previously published clinical trials. Results A consisting eight ( TP53 , KRAS STK11 EGFR PTPRD KMT2C SMAD4 HGF ) generated classify into high low groups cohort. Patients longer progression-free survival (hazard ratio (HR) 0.41, 0.28–0.61, p < 0.0001) overall (HR 0.53, 0.32–0.89, = 0.0275) compared GMS. noted equivalent findings validation demonstrated as factor for therapy comparing tumor mutational burden. Meanwhile, showed undifferentiated value different clinicopathological features. Notably, both PD-L1 predictors poorly correlated; inclusion further improved capacity PD-1 Conclusions Our study highlights immunotherapeutic benefit NSCLC. Besides, combination may serve optimal partner guiding treatment decisions