Comutations in DDR Pathways Predict Atezolizumab Response in Non-Small Cell Lung Cancer Patients

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.