Real-world outcomes with atezolizumab versus durvalumab plus chemotherapy for extensive-stage small cell lung cancer: A TriNetX propensity-matched analysis.

11145 Background: First-line treatment for extensive-stage small cell lung cancer (ES-SCLC) consists of platinum-etoposide plus an immune checkpoint inhibitor (ICI), either atezolizumab or durvalumab. No head-to-head randomized trials have compared these regimens. We evaluated real-world outcomes associated with these ICIs using a large multi-institutional database. Methods: We performed a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with ES-SCLC treated with platinum-etoposide plus atezolizumab or durvalumab were included. The index date was initiation of platinum, etoposide, and ICI therapy. Cohorts were matched 1:1 using propensity scores based on age, sex, race, tobacco use, and comorbidities. The primary outcomes were overall survival (OS) and real-world progression-free survival (rwPFS), defined as time to second-line therapy or death. Survival was analyzed using the Kaplan-Meier method and cox proportional hazards models. Secondary endpoints were immune-related adverse events (irAEs) and hospitalization rates and evaluated by z-test. The study protocol was created and reviewed by the authors prior to implementation and did not require IRB approval. Results: Among 750 eligible patients (677 atezolizumab, 73 durvalumab), 69 matched pairs were identified. Median follow-up was 13.4 months for atezolizumab and 8.6 months for durvalumab. Median OS was significantly longer with durvalumab compared with atezolizumab (23.2 vs 9.1 months; Hazard Ratio HR 0.58, 95% CI 0.47–0.93; p=0.021). No significant difference in rwPFS was observed (8.6 vs 6.7 months; HR 0.72, 95% CI 0.47–1.11; p=0.14) as shown in Table 1. Atezolizumab was associated with higher rates of hematologic adverse events (35 vs 22 events; p=0.025) and a trend toward increased hospitalizations (34 vs 24; p=0.085). No significant differences were observed in other irAE categories. Conclusions: This retrospective real-world analysis found that durvalumab-based first-line therapy was associated with longer OS compared to atezolizumab in patients with ES-SCLC, although no significant difference in rwPFS was observed. Interpretation is limited by shorter follow-up duration in the durvalumab cohort, which may contribute to observed survival differences. Due to the observational study design, potential residual confounding, and limited sample size, these results should be regarded as hypothesis-generating. These findings underscore the need for additional comparative effectiveness research to clarify optimal immunotherapy selection in ES-SCLC. Outcomes in propensity-matched cohort. Outcomes Atezolizumab Durvalumab Effect Estimate Patients (n) 69 69 Median OS (months) 9.1 23.2 HR 0.58 (95% CI 0.47–0.93) Median rwPFS (months) 6.7 8.6 HR 0.72 (95% CI 0.47–1.11)