Abstract
BACKGROUND: Docetaxel, following progression on immunotherapy and platinum-based chemotherapy, remains the standard of care for advanced non-small-cell lung cancer (NSCLC) but offers limited promise. Antibody-drug conjugates (ADCs) may improve outcomes in this population. OBJECTIVES: Data from the literature, mainly randomized controlled trials (RCTs), have shown discrepancies. This report evaluates the efficacy and safety of ADCs versus docetaxel in previously treated advanced NSCLC. DESIGN: The systematic review and meta-analysis was conducted focusing on phase II/III RCTs to synthesize available evidence regarding efficacy outcomes and safety of ADCs compared to docetaxel. DATA RESOURCES AND METHODS: Databases (PubMed (MEDLINE), EMBASE, and Cochrane Library), clinical trial registries, and proceedings of global oncology conferences from January 2015 to November 2024 were screened comparing ADC versus docetaxel. Two researchers independently completed data retrieval and screening work using Covidence. The Cochrane Risk of Bias Tool (RoB 2.0) was used to assess the methodological quality of the included RCTs. The primary outcomes include progression-free survival (PFS) and overall survival (OS), while the secondary outcomes include objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The pooled hazard ratios (HRs) and odds ratios (ORs) were meta-analyzed using the appropriate generic variance and Mantel-Haenszel methods. Random-effect models were used to compute pooled estimates. RESULTS: Of the 212 records screened, three RCTs involving 1597 patients were included. ADCs did not significantly improve PFS (pooled HR: 0.91, 95% CI: 0.73-1.13). For OS, the pooled HR was 0.88 (95% CI: 0.78-1.00, p = 0.06), reflecting a borderline significant trend favoring ADCs, with negligible heterogeneity (I (2) = 0%). Furthermore, subgroup analysis demonstrated a significant OS benefit in the nonsquamous cohort (HR: 0.85, 95% CI: 0.74-0.98, p = 0.03). In addition, no difference was observed in ORR (OR: 1.16, 95% CI: 0.54-2.51) and DCR (OR: 1.39, 95% CI: 0.75-2.57). Grade ⩾ 3 treatment-related AEs were significantly lower (pooled OR: 0.49, 95% CI: 0.26-0.90, p = 0.02) with ADCs, despite high heterogeneity (I (2) = 87%). CONCLUSION: Overall, there was no difference between the docetaxel and the ADC treatment arms; however, our findings report a significant survival benefit in the subgroup of patients with nonsquamous NSCLC pathology treated with ADCs compared to docetaxel with a manageable safety profile. Further research is needed to address heterogeneity, refine patient selection, and obtain more mature survival data with predictive biomarkers.