Time-dependent indirect comparison of enfortumab vedotin plus pembrolizumab and disitamab vedotin plus toripalimab in advanced urothelial carcinoma

Enfortumab vedotin plus pembrolizumab (EV-P) and disitamab vedotin plus toripalimab (DV-T) improved first-line outcomes in the global phase III EV-302/KEYNOTE-A39 trial (all-comer population) and the Chinese phase III RC48-C016 trial (HER2-expressing tumours), respectively, but no head-to-head comparison is available. We reconstructed individual patient data from published overall survival (OS) and progression-free survival (PFS) Kaplan-Meier curves and performed time-dependent anchored indirect comparisons through the randomised platinum-gemcitabine control arms. Anchored PFS ratios of treatment hazard ratios (RHRs) were 1.41 (95% CI 0.86-2.30), 1.02 (0.63-1.66) and 0.62 (0.20-1.89) at 0-6, 6-12 and 12-18 months. Corresponding OS RHRs were 0.78 (0.36-1.66), 1.07 (0.61-1.88), 0.74 (0.34-1.62) and 0.48 (0.16-1.47) through 24 months. Continuous spline analyses suggested declining PFS RHRs over time, whereas OS showed no consistent pattern; all 95% CIs included 1. Population heterogeneity limits transitivity. These exploratory findings do not establish superiority, equivalence or interchangeability.