A retrospective analysis of tarlatamab outcomes and safety in a global multicenter electronic health record network (TriNetX) database.

Abstract

e20167 Background: Tarlatamab, a bispecific T-cell engager (BiTE) targeting Delta-like Ligand 3 (DLL3), has been approved for the treatment of relapsed Extensive-stage Small Cell Lung Cancer (ES-SCLC). However, trial populations often exclude patients with active central nervous system (CNS) metastases or poor performance status. Real-world evidence is needed to characterize outcomes and safety of Tarlatamab in a broader patient population. Methods: We conducted a retrospective, propensity score-matched cohort study using a multi-center electronic health record network including 170 health care organizations globally (TriNetX). Adult patients with ES-SCLC who received tarlatamab were included and stratified by chemotherapy-free interval (CFI): “chemotherapy-free” (≥ 90 days) or “early chemotherapy” ( < 90 days). Cohorts were matched 1:1 on baseline demographic and clinical characteristics, Outcomes included overall survival (OS), CRS, and ICANS toxicities. Risk estimates and time-to-event analyses with Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results: The total cohort in this dataset had 658 patients. Table 1 included baseline characteristics. Safety analysis of the total cohort revealed an overall CRS incidence of 27.66% (Grade 1/2: 19.45%; Grade 3-5:1.98%; unspecified: 9.52%) and an overall ICANS incidence of 16.41% (Grade 1/2: 7.75%; Grade 3-5: 1.67%; unspecified: 10.33%), with 100% of events occurring within 14 days of the first dose. Tarlatamab was utilized as 2nd-line (28.9%), 3rd-line (24.0%), or 4th-line or greater (12.5%) with (34.6%) not reported. With a median follow-up of 18 months, the median OS for the whole cohort was 15.2 months. In the propensity score-matched analysis (n = 430, 215 patients per group), the chemo-free group showed a significant survival advantage (HR 0.691; 95% CI, 0.495–0.965), while toxicity remained comparable between matched groups for Grade 1/2 CRS (OR 0.971) and Grade 1/2 ICANS (OR 1.205). Conclusions: This large real-world analysis demonstrated outcome and safety data of tarlatamab in a diverse ES-SCLC population, demonstrating a median overall survival of 15.2 months. Safety profiles were lower than reported in clinical trials, with earlier median onset CRS and ICANS possibly due to reporting bias. Subgroup analysis identified a significant survival benefit for patients initiating tarlatamab after a chemotherapy-free interval of ≥ 90 days (HR 0.691), suggesting a potential biomarker for tarlatamab efficacy. However, additional mechanistic studies are needed to elucidate the role tumor biology and immune environment in this setting. that treatment sequencing to allow for immune recovery may optimize BiTE efficacy. Patient cohort N=658 Female % 51.27 Male % 48.73 Median age 67 Geographic distributionUSOutside US 93.5%6.5% History of brain metastases 42.2%(278)