Sequential Chemoradiotherapy Combined with Immunotherapy Versus Sequential Chemoradiotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: A Multicenter Retrospective Cohort Study with Propensity Score Matching

We aimed to assess the real-world effectiveness and toxicity of immune checkpoint inhibitor (ICI) treatment in unresectable stage III non-small cell lung cancer (NSCLC) patients who received ICIs before and after sequential chemoradiotherapy (sCRT) versus those who received sCRT alone.The study's primary endpoint was to evaluate the survival benefits of the treatment approach, with a focus on progression-free survival (PFS) and overall survival (OS), as well as treatment-related adverse events. From February 2018 to January 2023, 1,604 patients from three institutions were evaluated. Of these, 115 patients received ICI treatment both before and after sCRT (I-sCRT group), while 201 patients received only sCRT, serving as a control group (sCRT group). The inclusion of ICI treatment markedly improved PFS compared to those who received sCRT alone (HR 0.48, 95% CI 0.38–0.61; log-rank p < 0.001). The median PFS was 16.7 months (95% CI 15.5–21.7) in the I-sCRT group versus 9.9 months (95% CI 9.4–11.9) in the sCRT group. OS was also significantly prolonged in I-sCRT group compared to sCRT group, with a median OS of 38.2 months (95% CI 33.2-NA) versus 27.1 months (95% CI 23.3–35.4) (HR 0.64, 95% CI 0.47–0.87; log-rank p  = 0.007). The overall safety profile of I-sCRT group was safe and controllable. The propensity score matching results before and after the analysis were consistent. Our analysis revealed a significant improvement in PFS and OS with the combination of ICI treatment administered both before and after sCRT, indicating an effective treatment strategy for patients with unresectable LA-NSCLC.