{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:48:08Z","timestamp":1778831288129,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>There is limited evidence concerning real-world efficacy of second-line (2L) treatment with immune checkpoint inhibitors (ICIs) in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we evaluated the efficacy of 2L-ICIs therapy in patients with ES-SCLC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective study, we included patients with ES-SCLC who experienced disease progression following first-line (1L) therapy and received 2L treatment between March 2019 and December 2023. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints included safety, the objective response rate (ORR), the disease control rate (DCR), and overall survival (OS). Survival analyses were conducted using Kaplan-Meier curves. One-to-one propensity score matching (PSM) was used to reduce confounding. Univariate and multivariate Cox regression analyses were conducted to identify factors associated with PFS and OS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 496 patients in this study; among them, 200 patients were in the 2L-ICIs group and 296 patients were in the 2L-non-ICIs group. The 2L-ICIs group demonstrated significantly longer PFS than the 2L-non-ICIs group (median PFS: 4.13 vs. 2.70 months; p &amp;lt; 0.001), and this benefit persisted after PSM (median PFS: 4.14 vs. 2.84 months; p &amp;lt; 0.001). The 2L-ICIs group also had a significantly higher ORR (ORR: 29.5% <jats:italic>vs<\/jats:italic>. 10.1%; p &amp;lt; 0.001) and DCR (DCR: 67.0% <jats:italic>vs<\/jats:italic>. 51.7%; p &amp;lt; 0.001). Treatment-related adverse events were comparable between the groups, with only one grade 3 rash reported in the 2L-ICIs group. Multivariate Cox regression identified liver metastases, the number of metastatic lesions, and the 1L-PFS as independent predictive factors for PFS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this study, 2L-ICIs demonstrate significant clinical benefits with acceptable toxicity in ES-SCLC patients who progressed after 1L therapy, supporting their use as a clinically actionable option.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1658017","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T05:30:42Z","timestamp":1758259842000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Real-world outcomes of immune checkpoint inhibitors as second-line therapy for extensive-stage small-cell lung cancer: a multicenter retrospective 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