Safety and efficacy outcomes of delta-like ligand 3 inhibitors for the treatment of solid tumors: A systematic review and single-arm meta-analysis

The aim of the present study was to evaluate the clinical curative effects and toxicity of existing delta-like ligand 3 (DLL3) inhibitors in advanced solid tumors with high DLL3 expression. A systematic search across major databases was performed, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and included clinical trials that assessed the efficacy and safety of DLL3 inhibitors in treating solid tumors. To be included, studies had to be randomized controlled trials (RCTs), quasi-RCTs, non-randomized comparative studies, single-arm trials and trials in which DLL3 inhibitors were used in both arms. The results of 21 trials, involving a total of 2,452 patients, which evaluated the efficacy of DLL3 inhibitors in treating solid tumors, were analyzed. The median overall survival was 6.54 months and the median progression-free survival (PFS) was 3.54 months. Combination immunotherapy demonstrated a longer PFS of 4.2 months compared with monotherapy, which had a PFS of 3.36 months. The disease control rate and objective response rate were 57 and 21%, respectively, with notable heterogeneity observed across studies. Adverse events were common, affecting 93% of patients, and included cytokine release syndrome (49%), thrombocytopenia (23%) and peripheral edema (28%), with variations depending on the specific inhibitor used. To conclude, DLL3 inhibitors hold promise for patients with elevated DLL3 expression in solid tumors; however, their efficacy and safety exhibit considerable variability, necessitating large-scale, phase III clinical trials to validate and refine therapeutic approaches. The present study was registered with PROSPERO (registration no. CRD42024561815).