Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma

Introduction Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. Materials and Methods We analyzed 377 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009–2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT+IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. Results Median age was 70 years; 71 (20%) received CPBT+IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT+IO patients. Three-year survival rates for CPBT+IO vs CPBT were: OS 67% vs 30% (P<0.001) and PFS 59% vs 35% (P=0.017). Three-year LRFS (P=0.137) and DMFS (P=0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P=0.001) and PFS (HR 0.56, P=0.030), but not LRFS (HR 0.61, P=0.121) or DMFS (HR 0.61, P=0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT+IO vs 17% CPBT, P=0.037). Conclusion This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.