Efficacy and safety analysis of immune checkpoint inhibitor rechallenge therapy in locally advanced and advanced non-small cell lung cancer: a retrospective study.

Background: Immune checkpoint inhibitors (ICIs) have dramatically changed the first-line treatment pattern of non-small cell lung cancer (NSCLC) without driver gene alterations. However, the optimal choice for second-line treatment after initial treatment with ICIs is unclear. This study aimed to clarify the efficacy and safety of ICI rechallenge therapy in locally advanced and advanced NSCLC. Methods: We retrospectively analyzed the histories of 224 patients with locally advanced or advanced NSCLC treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy and/or antiangiogenic therapy in first-line treatment. Progression-free survival 2 (PFS2) was the time from the first defined progress disease (PD) to the second disease progression or death. Efficacy evaluation was performed directly in accordance with RECIST v1.1 criteria. Adverse events (AEs) were graded following the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Survival data were estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test in overall cohort and other subgroups. Results: There were no significant differences in objective response rate (ORR) and median PFS2 (mPFS2) between the ICI rechallenge group and non-rechallenge group (ORR: 10.3% Conclusions: ICI rechallenge therapy beyond disease progression did not improve clinical outcomes in patients with NSCLC, but no new safety signals emerged. However, patients with favorable response to initial ICIs treatment still showed significant efficacy of subsequent ICI rechallenge therapy.