Immunotherapy rechallenge in extensive-stage small-cell lung cancer: A real-world retrospective study.

e20130 Background: Although extensive-stage small-cell lung cancer (ES-SCLC) is highly sensitive to first-line immunotherapy combined with chemotherapy, most patients experience relapse and resistance after initial treatment. The median overall survival (mOS) with second-line chemotherapy is only 4–6 months. To date, there is a lack of prospective clinical trial data with a sufficient sample size to support the safety and efficacy of ICI rechallenge after progression on first-line immunotherapy in patients with ES-SCLC. Methods: This study retrospectively analyzed the clinical data of 151 patients with ES-SCLC who received first-line immunotherapy at Hunan Cancer Hospital between September 2019 and April 2025. We compared the efficacy and safety between patients who received ICI rechallenge (ICI rechallenge group, N = 100) and those who did not (non-ICI group, N = 51). The assessed endpoints included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: The ICI rechallenge group showed significantly higher ORR and DCR compared with the non-ICI group (ORR: 26.00% vs. 11.76%, p = 0.043; DCR: 75.00% vs. 47.06%, p < 0.001). The ICI rechallenge group also showed significantly longer PFS and OS compared with the non-ICI group (median progression-free survival [mPFS]: 3.98 vs. 2.43 months, p < 0.001; mOS: 9.43 vs. 6.23 months, p < 0.001). Subgroup analyses indicated that patients benefited from ICI rechallenge, regardless of the ICI rechallenge mode, ICI type, or combination regimen, compared with the non-ICI group. Multivariate Cox regression analysis confirmed that first-line PFS (1L-PFS) > 6 months and ICI rechallenge were independent protective factors (PFS: HR = 0.35, p < 0.001; OS: HR = 0.37, p < 0.001). Regarding safety, the incidence of grade ≥ 3 treatment-related adverse events (TRAEs) was not significantly different between the two groups (18.0% vs. 15.7%, p = 0.722). In the ICI rechallenge group, immune-related adverse events (irAEs) were predominantly grade 1–2. Grade ≥ 3 irAEs occurred in only 2.0% of patients. Conclusions: This real-world evidence confirms that ICI rechallenge significantly improves efficacy and prognosis in patients with ES-SCLC who progress after first-line immunotherapy combined with chemotherapy. The safety profile of ICI rechallenge is manageable. Regardless of the ICI rechallenge mode, ICI type, or combination regimen, patients with ES-SCLC can benefit from ICI rechallenge. This study provides critical evidence for clinical decision-making.