Evaluating the safety of antibody-drug conjugates in lung cancer: A systematic review and meta-analysis

Background: Antibody-drug conjugates (ADC) have emerged as a promising treatment for lung cancer. However, their safety profile requires further analysis. This study assessed adverse events (AE) in patients with lung cancer treated with ADCs, with particular focus on differences in pathological types, therapeutic options, and drug components. Methods: Prospective trials from various databases up to June 11, 2024, that analyzed treatment-emergent AEs (TEAEs), treatment-related AEs (TRAEs), mortality, and drug discontinuation were identified. Incidence rates were pooled using a random effects model, and their corresponding 95% confidence intervals (CIs) were calculated. Results: The analysis included 28 studies with 3,127 participants. The pooled incidence of all-grade TEAEs and TRAEs was 98.9 % and 91.4 %, respectively, whereas that of grade >= 3 TEAEs and TRAEs was 65.9 % and 41.7 %, respectively. The gastrointestinal system was frequently involved, albeit predominantly in low grades. Hematological system involvement was prevalent in grade >= 3 AEs, with respiratory system disorders being more prevalent in severe AEs. Respiratory system disorders were the primary cause of death and drug discontinuation. Subgroup analyses revealed higher incidences of AEs in SCLC than in NSCLC, in combination therapies than in monotherapies, and in ADCs with cleavable linkers. ADCs targeting delta-like protein 3 or carrying pyrrolobenzodiazepine dimer as payloads exhibit higher incidences of grade >= 3 TEAEs than those targeting HER2. Conclusion: Effective managing ADC toxicities is crucial in lung cancer treatment, with AE incidence and profiles varying by cancer pathology, treatment regimen, and ADC components. Close monitoring of symptoms associated with gastrointestinal, infection, and respiratory systems is essential. PROSPERO registration number: CRD42024546210