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.