Sequential versus concurrent strategy of immunotherapy and radiotherapy in advanced non-small-cell lung cancer: A territory-wide multicenter study (OCEANUS study).

8073 Background: Combination of immunotherapy with radiotherapy (iRT) has been a hot topic of research during last 10+ years with controversial results. In advanced non-small cell lung cancer (NSCLC), the optimal combination of iRT is not clear in the PACIFIC series of study. Using a prospective territory-wide multicenter study, this OCEANUS study aimed to compare the survival between sequential and concurrent iRT in locally advanced NSCLC. Methods: This real-world evidence study evaluated NSCLC patients treated in Hong Kong between January 1, 2010, and December 31, 2021. Patients diagnosed with unresectable locally advanced, de novo metastatic, or progressive NSCLC who received at least one cycle of immunotherapy combined with radiotherapy were included. The primary endpoint was real-world overall survival (rwOS). Survival outcomes were compared across various iRT combinations, with a focus on the impact of iRT strategies (concurrent versus sequential), the iRT time interval, and immune checkpoint inhibitor (ICI) maintenance duration. Results: A total of 3,522 patients received immunotherapy, of whom 338 underwent iRT (151 with initial iRT and 187 with salvage iRT). Patients who received iRT had significantly better overall survival (OS) compared to those who did not. Sequential iRT demonstrated significantly superior survival compared to concurrent iRT, with a 5-year rwOS of 45.3% (95% CI, 35.6–57.7%) versus 15.7% (95% CI, 7.2–33.8%; HR, 0.587; 95% CI, 0.382–0.901; P = 0.014). For salvage iRT, radiotherapy combined with maintenance ICIs achieved a median rwOS of 11.7 months (95% CI, 7.4–15.5), outperforming RT administered after ICI discontinuation (HR, 0.679; 95% CI, 0.470–0.979; P = 0.014). Shorter iRT intervals (<1 week) and 1 year of ICI maintenance were associated with additional survival benefits. Conclusions: The OCEANUS study provides significant real-world evidence supporting sequential iRT as the preferred strategy for unresectable locally advanced and de novo metastatic NSCLC. Salvage RT combined with maintenance ICIs was associated with improved rwOS in patients with progressive NSCLC. These findings offer actionable insights for optimizing iRT strategies in advanced NSCLC.