Induction Immunotherapy vs. Consolidation Immunotherapy for Unresectable Stage III NSCLC

Abstract

Consolidation immunotherapy after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). However, whether upfront immunotherapy before CRT has similar benefits has not been addressed. This study aimed at exploring the efficacy and safety of induction immunotherapy for unresectable stage III NSCLC through real-world data. Patients diagnosed with stage III NSCLC who received immunotherapy in combination with sequential (sCRT) or concurrent CRT (cCRT) between November 2018 and December 2021 were retrospectively identified. Patients were divided into induction (Ind), consolidation (Con) and induction plus consolidation (Ind+Con) immunotherapy groups. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and estimated by Kaplan‒Meier method. The potential factors affecting PFS and OS were analyzed by univariate and multivariate Cox regression models. One hundred and two patients were included, with 52 (51.0%) patients in the Ind group, 35 (34.3%) in the Con group and 15 (14.7%) in the Ind+Con group. Median PFS was 24.0 months vs. 36.0 months vs. 19.0 months in the three groups, and 2-year PFS were 43.0% vs 51.1% vs 44.4% (p = 0.940). Median OS was not reached (NR) vs. 44.0 months vs. NR, with a 2-year OS rate of 80.5% vs. 84.4% vs. 86.2% (p = 0.861). In the cCRT setting, 2-year PFS rates were 56.7% vs. 71.6% vs. 100.0% (p = 0.439), 2-year OS rates were 92.3% vs. 89.3% vs. 100.0% in the three groups (p = 0.827). In multivariate analysis, elder (HR = 0.487, p = 0.037) and cCRT (HR = 0.282, p = 0.001) were the independent factors favoring PFS, while only elder (HR = 0.088, p = 0.021) was the independent factors favoring OS. Adverse events were similar in the three arms. Further analysis found the objective response rate (ORR) and disease control rate (DCR) in the Ind and Ind+Con group after induction immunotherapy were 59.7% and 98.5%, respectively. Only 1 (1.5%) patient developed progression. Subgroup analysis showed no significant difference in PFS (p = 0.520) and OS (p = 0.116) between patients who responded to induction immunotherapy (PR+CR) and those who did not (SD+PD). Patients with <4 cycles of induction immunotherapy exhibited numerically better PFS than those with ≥4 cycles of induction immunotherapy (p = 0.113) and improved OS (p = 0.021). Induction immunotherapy may achieve similar survival benefits to consolidation immunotherapy, and the combination of induction and consolidation immunotherapy with cCRT appears to achieve better outcomes. It seems feasible and safe to upfront immunotherapy before CRT, and further investigations on the combination of induction immunotherapy and CRT are warranted.