This retrospective cohort study (TriNetX database, April 2024–May 2026) examined how ten classes of concomitant medications (used within 3 months of tarlatamab initiation) affected overall survival (OS), cytokine release syndrome (CRS), and ICANS in adults with extensive-stage small cell lung cancer (ES-SCLC).
Five medication classes were independently associated with significantly worse OS after propensity matching: antibiotics (HR 3.20, 95% CI 2.12–4.84), opioids (HR 2.84, 95% CI 1.71–4.70), acetaminophen (HR 2.26, 95% CI 1.23–4.14), glucocorticosteroids (HR 2.14, 95% CI 1.30–3.52), and benzodiazepines (HR 1.55, 95% CI 1.06–2.27); no medication class significantly affected ICANS.
Residual confounding cannot be excluded because some concomitant medications likely serve as proxies for disease severity or symptom burden rather than being causal; the retrospective, database-driven design limits causal inference; and cohort sizes per matched arm were relatively small (112–229).
Clinicians should be aware that several commonly used medications—especially antibiotics, opioids, acetaminophen, glucocorticosteroids, and benzodiazepines—are associated with worse survival in ES-SCLC patients on tarlatamab, though causality is unproven; these findings warrant prospective study before changing prescribing practice.
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