Comutations in DDR Pathways Predict Atezolizumab Response in Non-Small Cell Lung Cancer Patients
Anning Xiong, Wei Nie, Yan Zhou, Changhui Li, Kai Gu, Ding Zhang, Shiqing Chen, Fengcai Wen, Hua Zhong, Baohui Han, Xueyan Zhang
Abstract
The presence of comutations (co-mut+) in DNA damage response and repair (DDR) pathways was associated with improved survival for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC). However, it remains unknown whether co-mut+ status could be a predictive biomarker for immunotherapy. We aimed to explore the predictive role of co-mut+ status in the efficacy of ICIs. A total of 853 NSCLC patients from OAK and POPLAR trials were included in the analyses for the relationship between co-mut status and clinical outcomes with atezolizumab treatment. In co-mut+ NSCLC patients, significantly prolonged progression-free survival (PFS) ( p = 0.004) and overall survival (OS) ( p < 0.001) were observed in atezolizumab over docetaxel. The interaction between co-mut status and treatment was significant for PFS ( p for interaction = 0.010) and OS ( p for interaction = 0.017). In patients with negative or low programmed death receptor-ligand 1 expression, co-mut+ status still predicted improved clinical outcomes from atezolizumab therapy. These findings suggested that co-mut status may be a promising predictor of ICI therapy in NSCLC.