Real-world evaluation of immunotherapy in multi-line treatment of small cell lung cancer

To assess the real-world efficacy and safety of immunotherapy in small cell lung cancer (SCLC) across multiple lines of treatment.

We conducted a single-center, retrospective cohort study analyzing clinical data from 397 SCLC patients treated at the Second People's Hospital of Yichang (January 2018-July 2024). Based on treatment strategies, patients were divided into four groups: (1) first-line immune checkpoint inhibitor (ICIs)-based combination therapy, (2) first-line chemotherapy, (3) later-line ICIs-based combination therapy after first-line chemotherapy, and (4) chemotherapy in all lines. Propensity score matching (PSM) was used to balance baseline characteristics. Survival outcomes and safety were evaluated.

After matching, baseline characteristics were comparable. In patients with extensive-stage SCLC (ES-SCLC), first-line ICIs‑based combination therapy significantly improved median overall survival (OS, 12.9 vs. 10.2 months; hazard ratio [HR] = 0.56, 95% CI 0.38-0.80; p = 0.00189) and median progression-free survival (PFS, 8.0 vs. 5.6 months; HR = 0.57, 95% CI 0.40-0.80; p = 0.00125) compared with chemotherapy alone. In the limited-stage cohort, first-line ICIs‑based combination therapy yielded numerically longer OSOS (40.0 vs. 15.5 months; p = 0.121), though results are preliminary and should be interpreted with caution given sample limitations. In the later-line setting, ICIs‑based combination therapy significantly extended median OS compared with chemotherapy (10.4 vs. 7.4 months; HR = 0.60, 95% CI 0.37-0.98; p = 0.0405). Exploratory analysis indicated longer OS with later-line versus first-line ICIs (22.6 vs. 12.6 months; HR = 2.44, 95% CI 1.12-5.33; p = 0.0255); however, this finding may be influenced by potential selection biases and guarantee-time bias and should be viewed as hypothesis-generating only. Immune-related adverse events (irAEs) occurred in 11.1-22.2%, indicating manageable toxicity.

Immunotherapy, whether first-line or later-line, improves survival in ES-SCLC with acceptable safety. Our exploratory results suggest that later-line immunotherapy may be associated with favorable survival trends; however, these findings are hypothesis-generating and require validation in prospective trials due to inherent selection biases.