Frontiers in Immunology (Sep 2021)

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

DOI
https://doi.org/10.3389/fimmu.2021.708558
Journal volume & issue
Vol. 12

Abstract

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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.

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