Comparison of concurrent chemoradiotherapy followed by immunotherapy and induction chemoimmunotherapy followed by radiotherapy in unresectable stage III NSCLC: a retrospective cohort study

Concurrent chemoradiotherapy followed by immune consolidation therapy (cCRT+IO, the PACIFIC regimen) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, the optimal timing of combining radiotherapy with immunotherapy remains unexplored. This study compared the efficacy and safety of induction chemoimmunotherapy followed by radiotherapy (ICT+RT) with cCRT+IO.
This study included patients with unresectable stage III NSCLC who received cCRT+IO or ICT+RT between January 2021 and August 2023. Efficacy outcomes and safety profiles were assessed.
A total of 183 eligible patients were enrolled; 108 (59.0%) received cCRT+IO, and 75 (41.0%) received ICT+RT. The median progression-free survival (PFS) was 26.8 months in the cCRT+IO group and 16.4 months in the ICT+RT group (hazard ratio [HR] 0.66; 95%CI 0.45–0.97; p = 0.031). The median overall survival (OS) was 45.4 months in the cCRT+IO group and was not reached in the ICT+RT group (HR 0.57, 95%CI 0.32–0.99; p = 0.046). In the cCRT+IO group, the incidence of grade 3 pneumonitis was 6.48%, whereas it was 13.33% in the ICT+RT group (p = 0.116).
Compared with ICT+RT, cCRT+IO demonstrated superior efficacy with a manageable safety profile in unresectable stage III NSCLC.
This study compared two treatment approaches for patients with stage III non-small cell lung cancer that cannot be removed by surgery. The first is the current standard treatment: chemotherapy and radiotherapy given at the same time, followed by immunotherapy. The second approach uses chemotherapy combined with immunotherapy first, then radiotherapy alone. We found the standard treatment helped patients live longer and was generally safe in clinical practice. While the immunotherapy-first approach may sound promising, it carried a higher risk of severe lung inflammation. This research provides practical evidence to help doctors and patients make more informed decisions on the optimal treatment sequence for this type of lung cancer.