Lack of Survival Benefit with Immunotherapy in Combination with Adjuvant Chemoradiation in Pathologic Stage II-IIIB Non-small Cell Lung Cancer

Background: Currently, atezolizumab and pembrolizumab are standard management for curatively resected stage II-III non-small cell lung cancer (NSCLC) owing to prior studies showing that they improve disease-free survival. However, these studies excluded the planned use of adjuvant radiation therapy. Survival benefit of adding immune checkpoint inhibitor (ICI) in patients treated with adjuvant chemoradiation (CT+RT) has not been fully assessed. Methods: Using National Cancer Database (NCDB), we identified and, based on therapy received, stratified 4,934 cases involving patients undergoing complete resection with pathologic stage II-IIIB NSCLC who survived at least 1 month without neoadjuvant CT or RT and subsequently received adjuvant chemotherapy. Kaplan-Meier methods and multi-variable Cox regression models were used for survival analysis. Propensity score matching was performed to compare adjuvant CT+RT+ICI vs. CT+RT. A p-value of <0.05 was considered statistically significant. Results: The addition of ICI to adjuvant CT improved overall survival (OS) (2-year OS 90.1% vs. 86%, univariate and multivariate hazard ratios [HRs] 0.72 and 0.66, p = 0.0024 and 0.0003, respectively). However, no OS benefit was seen in those who received adjuvant CT+RT (2-year OS 77.8% vs. 76.1%, univariate and multivariate HRs 0.83 and 0.85, p = 0.3677 and 0.4369, respectively). Propensity score matching analysis showed similar results (2-year OS 77.8% vs. 79.6%, univariate and multivariate HRs 0.91 and 0.87, p = 0.7143 and 0.5868, respectively). Conclusions: Our retrospective real-world analysis suggests that adjuvant ICIs do not improve survival outcome when combined with adjuvant CT+RT. This result mirrors recent negative trials studying ICI+CT+RT in unresectable stage III NSCLC and limited-stage SCLC. Further investigations are warranted.