Retrospective cohort study of associations of concomitant medications with outcomes of tarlatamab for extensive-stage small cell lung cancer

Tarlatamab is a bispecific T-cell engager (BiTE) with efficacy in extensive-stage small cell lung cancer (ES-SCLC). A retrospective study using TriNetX between April 2024 and May 2026 evaluated the association of commonly prescribed concomitant (between 3 months before and 3 months after tarlatamab initiation) medications with outcomes in patients receiving tarlatamab for ES-SCLC. The primary endpoint was overall survival (OS), while secondary endpoints were cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). One-to-one propensity score matchning was performed for demographics, comorbidities, disease characteristics, prior therapies, and the remaining nine medication classes. Among ten propensity-matched comparisons, cohort sizes ranged from 112 to 229 per arm. Five medication classes were associated with significantly worse OS: antibiotics (HR 3.20; 95% CI 2.12-4.84), opioids (2.84; 1.71-4.70), acetaminophen (2.26; 1.23-4.14), glucocorticosteroids (2.14;1.30-3.52), and benzodiazepines (1.55; 1.06-2.27). Acetaminophen was uniquely associated with increased CRS risk (HR 2.08; 95% CI 1.13-3.82), whereas no medication class significantly affected ICANS. The authors conclude that several commonly used medications were associated with inferior survival in patients receiving tarlatamab for ES-SCLC. Although residual confounding cannot be excluded, these findings support prospective investigation of concomitant medication use during BiTE therapy.