Immune checkpoint inhibitor‑based vs. non‑immunotherapy subsequent treatment after progression on first‑line chemoimmunotherapy in extensive‑stage small cell lung cancer: A meta‑analysis

First-line chemoimmunotherapy is currently a standard treatment for extensive-stage small cell lung cancer (ES-SCLC), but the value of immune checkpoint inhibitor (ICI)-based subsequent treatment after progression remains uncertain.The present meta-analysis assessed the efficacy and safety of ICI-based vs. non-immunotherapy subsequent treatment after progression on first-line chemoimmunotherapy.The present systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement.The PubMed, Embase, Web of Science Core Collection, Scopus and Cochrane Library databases were searched from their respective dates of inception to May 8, 2026.Comparative studies evaluating ICI-based vs. non-immunotherapy subsequent treatment after progression on first-line chemoimmunotherapy in ES-SCLC were eligible for inclusion.The primary outcomes were overall survival (OS) and progression-free survival (PFS).Secondary outcomes included objective response rate (ORR), disease control rate (DCR) and grade ≥3 adverse events (AEs) or treatment-related AEs (TRAEs).Hazard ratios (HRs) and risk ratios (RRs) with 95% CIs were pooled using random-effects models.A total of 10 non-randomized comparative studies, including nine retrospective clinical real-world cohorts and one retrospective translational cohort analysis, were included.Among these, six studies contributed to the primary OS and PFS meta-analyses, whereas the remaining four were included in qualitative synthesis or sensitivity analyses because of incomplete eligibility alignment or non-poolable estimates.Compared with non-immunotherapy subsequent treatment, ICI-based subsequent treatment was associated with longer OS (HR, 0.62; 95% CI, 0.51-0.74;P<0.00001) and PFS (HR, 0.51; 95% CI, 0.38-0.69;P<0.0001).The survival associations remained stable in sensitivity analyses using unmatched estimates or additional partially aligned datasets.ICI-based subsequent treatment was also associated with higher ORR (RR, 2.31; 95% CI, 1.61-3.32;P<0.00001) and DCR (RR, 1.51; 95% CI, 1.16-1.98;P=0.003).No significant increase in grade ≥3 AEs or TRAEs was observed (RR, 0.89; 95% CI, 0.56-1.40;P= 0.61).To conclude, these findings suggest that ICI-based subsequent treatment was associated with more favorable survival and tumor-response outcomes after progression on first-line chemoimmunotherapy in ES-SCLC, without evidence of a clear increase in severe toxicity.However, given that all included studies were non-randomized comparative studies, with potential treatment-selection bias and regimen heterogeneity, the present findings require prospective validation. Immune checkpoint inhibitor-based vs. non-immunotherapy subsequent treatment after progression on first-line chemoimmunotherapy in extensive-stage small cell lung cancer: A meta-analysis