Real-World Effectiveness and Safety of Tarlatamab in Pretreated Small Cell Lung Cancer

A systematic review synthesized real-world data regarding the effectiveness and safety of tarlatamab, a delta-like ligand 3 (DLL3)-targeted bispecific T-cell engager, in routine clinical practice for pretreated small cell lung cancer (SCLC). Following PRISMA 2020 guidelines and PROSPERO registration (CRD420261345046), searches of PubMed, the Cochrane Library, and ScienceDirect yielded five retrospective observational studies meeting inclusion criteria out of 134 screened records. Due to heterogeneity in patient characteristics, outcome definitions, and follow-up, findings were synthesized narratively.

Across selected predominantly de novo SCLC cohorts, reported partial or objective response rates ranged from 35.2% to 66.7%, with rates frequently evaluated only in response-evaluable subsets. In one cohort reporting an objective response rate of 66.7% (20/30 evaluable patients), documented responses occurred in 41.7% (20/48) of all treated individuals. Across reported analyses, median progression-free survival ranged between 1.7 and 4.9 months. Outcomes were less favorable in patients with EGFR-mutant transformed SCLC, who achieved a partial response proportion of 7.1% (1/14 evaluable patients) and a median overall survival of 2.7 months.

Regarding safety, cytokine release syndrome occurred in 54.2% to 72.7% of patients across selected cohorts, and immune effector cell-associated neurotoxicity syndrome (ICANS) was documented in 23.3% to 47.6%, reflecting substantial variation across populations and protocols. The authors noted that the overall certainty of evidence was very low, with effectiveness estimates constrained by small sample sizes, evaluation limited to response-evaluable subgroups, and variable toxicity ascertainment, indicating the need for prospective studies to establish real-world effectiveness and optimize toxicity management.