Assessment of survival benefit with immunotherapy in combination with adjuvant chemoradiation in pathologic stage II-IIIB non-small cell lung cancer.

Abstract

8018 Background: Since the Food and Drug Administration (FDA) approvals in 2021 and 2023, atezolizumab and pembrolizumab, respectively, became standard management for curatively resected stage II-III non-small cell lung cancer (NSCLC) based on improved disease-free survival. Because these studies excluded the planned use of adjuvant radiation therapy, survival benefit of adding immune checkpoint inhibitor (ICI) in those who are treated with adjuvant chemoradiation (CT+RT) have never been assessed. Methods: Using National Cancer Database (NCDB), we identified 8,235 cases that were completely resected, pathologic stage II-IIIB NSCLC per AJCC 8 th edition and survived for at least 1 month without neoadjuvant CT or RT. Due to the timing of FDA approval and availability, only cases diagnosed in 2021 were investigated. They have been assigned into groups based on types of adjuvant treatments. Kaplan-Meier methods and multi-variable Cox regression models were used for survival analysis. Propensity Score Matching (PSM) was performed to compare groups (adjuvant CT+RT+ICI vs CT+RT). A p-value of <0.05 was considered statistically significant. Results: Consistent with previous clinical trials, addition of ICI to adjuvant CT improved overall survival (OS) (2-year OS 90.1% vs 86.0%, Univariate and Multivariate 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). PSM 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 ICI do not improve survival outcome when combined with adjuvant CT+RT. This result appears to mirror recent negative trials using concurrent use of ICI with CT+RT in unresectable stage III NSCLC (PACIFIC2) and limited-stage SCLC (NRG-LU005). Further investigations are warranted. Overall survival of p-stage II-IIIB NSCLC treated with designated therapy regimens. Groups Adjuvant CT+ICI Adjuvant CT Adjuvant CT+RT+ICI Adjuvant CT+RT N 3,549 878 132 375 2-year OS (month) 90.1% 86.0% 77.8% 76.1% Univariate HR (95%CI) 0.72 (0.57-0.89) 0.83 (0.55-1.23) p-value (Log-rank) 0.0034 0.3744