Objective: To indirectly compare the efficacy of standard of care (SoC) treatments in 1L mUC by synthesizing evidence available from the clinical literature.

Methods: Based on clinical guidelines and input from clinical experts, treatments were categorized according to patients’ tolerance/eligibility for cisplatin-based chemotherapy and programmed death-[ligand] 1 (PD-[L]1) inhibitors: I) For cisplatin-eligible patients: cisplatin+gemcitabine (CIS+GEM), methotrexate+vinblastine+doxorubicin+cisplatin (MVAC) and high-dose MVAC (HD-MVAC); II) For cisplatin-ineligible patients: carboplatin+gemcitabine (CAR+GEM); III) For cisplatin-ineligible PD-L1+ patients: CAR+GEM, atezolizumab and pembrolizumab monotherapies. A systematic literature review identified relevant 1L mUC trials to inform survival analyses. Available data in group III were sparse in terms of patients’ PD-L1 expression and cisplatin eligibility. Survival analyses fitted parametric and spline-based models to the reconstructed survival data from the pivotal trials of each reference SoC treatment in each group, whereas Bayesian ITCs estimated relative treatment effects across treatments via constant hazard ratios (HR).

Results: In all groups, spline-based models with hazard timescale (2-knots for group I and 1-knot for groups II and III) performed the best both statistically and visually. Reference SoC survival was estimated by extrapolating the data from CIS+GEM arm of EORTC-30987 study for group I, and from CAR+GEM arm of EORTC-30986 study for groups II and III. The 40-year restricted mean survival was estimated to be 3 years with CIS+GEM and 1 year with CAR+GEM. Post-ITC, the most efficacious treatments in groups I and III were HD-MVAC (HRs w/95% credible intervals [CrI]: 0.77 [0.58-0.99] vs. MVAC and 0.71 [0.50-0.98] vs. CIS+GEM) and atezolizumab (HRs w/95% CrIs: 0.70 [0.43-1.08] vs. CAR+GEM and 0.70 [0.40-1.15] vs. pembrolizumab).

Conclusions: The extrapolations and ITC-adjusted estimates for relative treatment effects allow pairwise comparisons of 1L mUC treatments. HD-MVAC showed improved efficacy versus CIS+GEM in group I, while no evidence for difference in efficacy across therapies was found in group III.