Tarlatamab in Small Cell Lung Cancer and Extrapulmonary Small Cell Carcinoma: A Single-Centre Retrospective Cohort Study of Routine-Practice Outcomes

BACKGROUND: Tarlatamab, a Delta-like ligand 3 (DLL3)-targeting bispecific T-cell engager (BiTE), has demonstrated significant efficacy in relapsed small cell lung cancer (SCLC) in clinical trials. However, real-world clinical outcomes and its efficacy in extrapulmonary small cell carcinoma (EPSCC) remain sparsely characterized. METHODS: We conducted a retrospective, single-institution cohort study of 24 adult patients with moderately pretreated advanced SCLC (n = 19) or EPSCC (n = 5) who received standard-of-care tarlatamab. Endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Patients had received a median of two prior lines of therapy, and 38% had baseline brain metastases. The overall intent-to-treat (ITT) ORR was 25.0%. Among response-evaluable patients (n = 18), the ORR was 33.3%. Efficacy was notably discordant between histologies: the SCLC cohort achieved an ITT ORR of 31.6% (46.2% in evaluable patients), whereas 100% of EPSCC patients experienced progressive disease. Systemic responses were observed in patients with baseline brain metastases (ORR 33.3%). The safety profile was manageable; any-grade CRS and ICANS occurred in 58% and 29% of patients, respectively. Severe (Grade ≥ 3) toxicities were rare, and tocilizumab was utilized therapeutically in 50% of patients for low-grade toxicity. CONCLUSIONS: These real-world data are consistent with tarlatamab's systemic efficacy and tolerability in SCLC. The lack of clinical benefit observed in this small EPSCC cohort raises a hypothesis that requires prospective biomarker-correlated evaluation.