DNA Damage Response Alterations Stratify Response to ICI-Based Therapy in Advanced NSCLC with High PD-L1 Expression
TL;DR
Patients with multiple DNA damage response gene alterations showed distinct immune profiles, higher rates of durable clinical benefit, and longer progression-free survival, and these findings suggest that genomic DNA damage response alterations may help identify patients who are more likely to benefit from personalized immunotherapy strategies.
Abstract
Simple Summary Immune checkpoint inhibitors have improved outcomes for patients with advanced non-small cell lung cancer, particularly those with high programmed death-ligand 1 expression. However, a proportion of patients derive limited benefit from these treatments, highlighting the need for additional biomarkers to guide therapeutic decisions. In this study, we investigated genomic alterations in the DNA damage response pathway and their association with immunotherapy outcomes in advanced non-small cell lung cancer. Patients with multiple DNA damage response gene alterations showed distinct immune profiles, higher rates of durable clinical benefit, and longer progression-free survival. They also appeared to derive greater benefit from combined chemotherapy and immunotherapy. These findings suggest that genomic DNA damage response alterations may help identify patients who are more likely to benefit from personalized immunotherapy strategies.