Radiotherapy improves outcomes in patients with NSCLC receiving nivolumab

BACKGROUND: Despite significant advances in systemic therapies, non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have improved outcomes in advanced disease, durable responses occur in only a subset of patients. Radiotherapy (RT) may enhance antitumor immunity by modulating the tumor microenvironment. This study aimed to evaluate the association between RT and survival outcomes in patients with advanced NSCLC treated with nivolumab. METHODS: This retrospective study included patients with advanced NSCLC who progressed after first-line platinum-based chemotherapy and received nivolumab as second-line therapy between January 2015 and January 2025. Patients who received RT before or during nivolumab, including RT for oligoprogression, were evaluated. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier estimates and Cox regression models. RESULTS: A total of 191 patients were included. The median age was 64 years (range, 37–83), and adenocarcinoma and squamous cell carcinoma accounted for 47.6% and 44% of cases, respectively. Median PFS and OS were 6.9 and 14.1 months, respectively. Patients who received RT had significantly longer PFS (11.9 vs. 3.6 months; p < 0.001) and OS (31.8 vs. 8.3 months; p < 0.001) compared with those who did not. Median PFS was not reached in patients receiving RT for oligoprogression, with 57% remaining progression-free at 6 months. Multivariate analysis identified ECOG performance status, RT history, and adrenal metastases as independent predictors of PFS, while ECOG performance status, prior surgery, RT history, and brain and adrenal metastases were independent predictors of OS. CONCLUSIONS: RT administered before or during nivolumab was associated with improved survival outcomes in advanced NSCLC. However, given the retrospective design and potential selection bias, these findings should be interpreted cautiously. Prospective studies are needed to clarify the optimal integration and timing of RT with ICIs.