Safety Evaluation of Tarlatamab in SCLC: A Systematic Review and Meta-Analysis

Tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 and CD3, demonstrated clinical activity both in previously treated SCLC and as intensification of maintenance immunotherapy. Owing to its action mechanism, tarlatamab exerts a new toxicity profile, needing careful management. Based on these premises, we performed a systematic review and meta-analysis to evaluate treatment-related adverse events (TRAEs) among available clinical trials enrolling patients with SCLC receiving tarlatamab monotherapy.

The research protocol was recorded in PROSPERO register with ID no. 1163787. We included the following keywords: phase I, phase II, phase III, small cell lung cancer, and tarlatamab. We conducted research in Embase, PubMed, Scopus, and Web of Science databases.

A total of four studies with 457 observations were included. Although Egger's test was performed, the results must be interpreted with caution as the small number of included studies (n = 4) limits the statistical power to reliably detect publication bias.For TRAEs, grades 3 to 4, 385 events were registered assessing the overall prevalence of 42% (95% confidence interval [CI]: 23%-64%). For serious TRAEs, 178 events were registered, and the overall prevalence was estimated at 40% (95% CI: 18%-67%). For TRAEs leading to dose interruptions and dose reduction, 105 events were included, and the prevalence was 24% (95% CI: 16%-34%). For TRAEs leading to discontinuation, 16 events were recorded, and the pooled prevalence was 4% (95% CI: 1.4%-8.2%). For TRAEs for grade 5 events, 12 events were analyzed, and the pooled prevalence was 3.2% (95% CI: 0.4%-22%). For cytokine release syndrome, 255 events were recorded, and the overall was 55.8% (95% CI: 48%-63%). For immune effector cell-associated neurotoxicity syndrome, 40 events were recorded, and the pooled prevalence was 8.9% (95% CI: 3.3%-21.8%). For decreased appetite, 146 events were reported, and the overall prevalence was 31% (95% CI: 23%-41%). For pyrexia, 139 events were analyzed, and the pooled prevalence was 30% (95% CI: 24%-38%). As regards dysgeusia, 457 observations and 139 cases were included, and the pooled prevalence was estimated at 32.5% (95% CI: 20%-48%).

Future research should be focused on identifying risk factors for TRAEs and developing prophylactic strategies to mitigate this risk without blunting antitumor efficacy in patients with SCLC receiving tarlatamab. By improving our understanding and management of tarlatamab TRAEs, we can maximize its clinical efficacy while minimizing harm and ultimately improving outcomes for patients with SCLC.