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.

DNA 损伤反应和修复 (DDR) 通路中突变 (co-mut+) 的存在与非小细胞肺癌 (NSCLC) 免疫检查点抑制剂 (ICI) 治疗的存活率提高有关。然而，目前尚不清楚 co-mut+ 状态是否可以作为免疫治疗的预测生物标志物。我们旨在探索 co-mut+ 状态在 ICI 疗效中的预测作用。共有 853 名来自 OAK 和 POPLAR 试验的 NSCLC 患者被纳入对 co-mut 状态与 atezolizumab 治疗临床结果之间关系的分析。在 co-mut+ NSCLC 患者中，显着延长了无进展生存期 (PFS) (p = 0.004) 和总生存期 (OS) (p< 0.001) 在 atezolizumab 中观察到超过多西他赛。co-mut 状态和治疗之间的相互作用对 PFS 是显着的（p 对于交互 = 0.010) 和 OS (p交互作用 = 0.017）。在程序性死亡受体-配体 1 表达为阴性或低表达的患者中，co-mut+ 状态仍可预测来自 atezolizumab 治疗的临床结果的改善。这些发现表明，co-mut 状态可能是 NSCLC 中 ICI 治疗的有希望的预测指标。