Systematic review and meta-analysis of studies of antibody-drug conjugates for locally advanced and metastatic urothelial carcinoma

Antibody-drug conjugates (ADCs), including enfortumab vedotin (EV), disitamab vedotin (DV), and sacituzumab govitecan (SG), are increasingly being used for locally advanced or metastatic urothelial carcinoma (la/mUC). A systematic review and meta-analysis of 40 interventional and observational studies involving 6085 adult la/mUC patients evaluated clinical outomes with ADCs. For EV monotherapy, the pooled objective response rate (ORR) was 43.9% (95% CI 40.4-47.5) in interventional studies and 44.6% (41.0-48.2) in observational studies. For EV plus pembrolizumab, interventional cohorts showed a pooled ORR of 67.5% (95% CI 63.5-71.3) overall and 65.4% (60.0-70.5) in cisplatin-ineligible patients. DV plus PD-1 inhibitors was associated with an ORR of 74.7% (95% CI 69.4-79.4) in interventional studies and 61.7% (52.6-70.1) in observational studies. The authors conclude that these findings suggest that EV-based regimens are associated with robust outcomes across clinical settings, and DV combinations are associated with potent clinical activity.