Real-world survival and safety outcomes of tarlatamab in patients with extensive stage small cell lung cancer.

e20168 Background: Tarlatamab, a DLL-3 targeted bispecific T cell engager targeting Delta-Like ligand 3 has shown promising clinical activity in relapsed, refractory extensive-stage small cell lung cancer (ES-SCLC). Toxicities included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. However, real-world data on survival and safety remains limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network Database. Patients with SCLC treated with tarlatamab were identified. Lung cancer diagnosis codes were combined with SCLC-specific histologic classifications. The index date was the first recorded tarlatamab administration. The primary outcome was overall survival (OS) and was assessed using Kaplan-Meier methods, with survival probabilities estimated at 6 months, 1 year, and 2 years. Treatment-related toxicities were evaluated in secondary analyses and included CRS, ICANS, pyrexia, and neutropenia. Results: 682 patients with ES-SCLC treated with tarlatamab were identified. Kaplan–Meier–estimated survival probabilities were 68.8% at 6 months, 54.6% at 1 year, and 46.2% at 2 years. The Kaplan–Meier survival curve did not cross the 50% threshold during the available follow-up period, and therefore median overall survival was not reached. The median observed survival time at 2 years was 417 days. Given the relatively short median follow-up compared with the 2-year survival horizon, longer-term survival estimates should be interpreted with caution. Treatment-related adverse events were evaluated within prespecified post-treatment time windows. Within the first 30 days following treatment initiation, pyrexia or CRS occurred in 287 patients (42.1%). ICANS was identified in 69 patients (10.1%), and neutropenia occurred in 52 patients (7.6%). Lower observed rates of CRS and neutropenia alongside a higher incidence of ICANS may be related to monitoring intensity and systematic toxicity assessment in trial settings. Conclusions: In this real-world large database analysis, tarlatamab demonstrated clinically meaningful overall survival and a manageable toxicity profile. These findings support the clinical effectiveness of tarlatamab outside of trial settings and underscore the importance of real-world evidence concerning novel bispecific therapies. Longer-term follow-up is needed to assess the durability of survival and late toxicities.