Efficacy of radiotherapy combined with atezolizumab or docetaxel in patients with previously treated NSCLC

Radiotherapy showed synergy with immunotherapy, yet the comparative effectiveness of combining immunotherapy (iRT) or chemotherapy (CRT) after platinum therapy failure in advanced non-small cell lung cancer (NSCLC) remains unexplored. We analyzed 163 patients (iRT: <i>n</i> = 120 vs. CRT: <i>n</i> = 43) eligible for combination radiotherapy. Before matching, median overall survival (OS) was significantly longer in iRT group (7.79 vs. 4.57 months, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41-0.94, <i>p</i> = 0.024). After 1:2 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW), iRT group showed improved OS, consistent with unmatched analysis (PSM, <i>p</i> = 0.033 and IPTW, <i>p</i> = 0.035). Exploratory analysis suggested that PD1⁺, central memory PD1⁺, and effector memory PD-L1⁺ CD4⁺ T cells were strong predictive biomarkers for iRT-treated patients (<i>P</i> _OS = 0.025, <i>P</i> _OS = 0.002, <i>P</i> _OS = 0.010, respectively). Proliferative CD4⁺ T cell_low was a prognostic (<i>P</i> _OS = 0.008) and predictive biomarker for iRT (<i>P</i> _OS < 0.001). Our work revealed iRT was prolonged OS in previously treated advanced NSCLC patients. Additionally, proliferative CD4⁺ T cell served as prognostic and predictive biomarkers.