Efficacy and safety of antibody-drug conjugates in the treatment of non-small cell lung cancer: a systematic review and meta-analysis of prospective clinical trials.

Background: Antibody-drug conjugates (ADCs) constitute an emerging class of targeted agents designed to deliver cytotoxic payloads selectively to tumor cells, thereby minimizing systemic toxicity. In non-small cell lung cancer (NSCLC), several ADC targets have demonstrated antitumor activity in early-phase clinical trials, particularly in the advanced/metastatic setting following progression on standard therapies. Nevertheless, the current evidence remains fragmented due to small sample sizes, single-arm study designs, and heterogeneous patient populations, which limits robust conclusions regarding their comparative efficacy and safety profiles. This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of ADCs for the treatment of advanced or metastatic NSCLC by analysing data from prospective clinical trials. These findings provide strong evidence supporting personalised clinical treatment strategies. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, EMBASE, the Cochrane Library, Web of Science, and conference proceedings for prospective trials published until 30 January 2025. Two researchers (X.J. and W.Z.) independently screened studies, extracted data, and assessed quality using the Cochrane Risk of Bias Assessment and Methodological index for non-randomised studies tool. Statistical analyses were performed with R 4.4.2 using a random-effects model, including heterogeneity (I Results: Thirteen prospective clinical studies were included, comprising five randomised controlled trials (RCTs) and eight single-arm cohort studies, involving 1,681 patients. The pooled overall response rate (ORR) was 0.30 [95% confidence interval (CI): 0.23-0.36; I Conclusions: Our analysis revealed that although ADCs demonstrate promising efficacy in advanced/metastatic NSCLC, the interpretability of these findings is constrained by significant interstudy heterogeneity. Current evidence lacks a clear superiority of ADCs monotherapy over standard chemotherapy. Future large-scale randomised trials should optimise the clinical use through combination approaches, subgroup efficacy analyses, and long-term safety assessments. Such studies are crucial to guide evidence-based strategies.