e20136 Background: Standard of care treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) includes a combination of chemotherapy (cisplatin or carboplatin plus etoposide) and a programed death ligand 1 (PD-L1) targeted monoclonal antibody. The use of immunotherapy has significantly improved overall survival (OS) for ES-SCLC patients. However, no head-to-head trials have addressed which immunotherapy provides superior outcomes in this population. To our knowledge, this is the first large-scale study that compares OS for patients who received Durvalumab vs Atezolizumab in their treatment for ES-SCLC. Methods: A retrospective cohort study using the TriNetX Research Network, a federated platform of HIPAA-compliant patient records from 158 healthcare organizations (HCO) from the Global Collaborative Network was carried out. We compared first-line outcomes of atezolizumab vs durvalumab in patients with ES-SCLC. Cohorts were balanced for age and sex. Overall survival (OS) was assessed via Kaplan-Meier analysis. Tarlatamab was excluded from primary analysis and evaluated in a separate secondary query. Results: From January 2019 to December 2025, 6,750 patients were identified across 113 HCOs for each balanced cohort. Durvalumab demonstrated superior OS compared to Atezolizumab p < 0.0001. Durvalumab patients had a lower risk of brain metastasis (OR 0.348). Brain metastasis at the time of diagnosis showed that patients who received Durvalumab maintained superior OS p < 0.0001. Patients who received messenger ribonucleic acid (mRNA) COVID vaccines within 100 days of initiation of the treatment had better OS than those who didn’t, an effect observed in both Durvalumab p = 0.0004 and Atezolizumab p < 0.001. In the vaccinated patients, Durvalumab demonstrated better OS. Survival probabilities for Durvalumab vs. Atezolizumab at 6, 12, and 24 months were 88% vs. 73%, 77% vs. 50%, and 64% vs. 33%, respectively. When patients received Tarlatamab, there was no longer a difference in OS regardless of the front-line treatment received. Conclusions: In ES-SCLC patients, Durvalumab had statistically superior OS compared to Atezolizumab. Although COVID mRNA vaccination improved overall outcomes, the survival advantage for Durvalumab remained. This benefit also persisted in patients with brain metastases. While PD-L1 inhibitors often show comparable effects across trials, this real-world database analysis revealed significant outcome differences warranting further investigation. Future analyses should evaluate the long-term effects of Tarlatamab as mature data becomes available, given its recent Food and Drug Administration approval. Although TriNetX relies on coding accuracy, survival exceeded those reported in pivotal trials, highlighting the need for prospective clinical trials to address this question for the treatment of ES-SCLC.
Velez et al. (Thu,) studied this question.