Objective:

To evaluate the overall survival (OS) of patients with metastatic urothelial carcinoma (mUC) receiving first-line therapy with enfortumab vedotin combined with pembrolizumab (EV/P) compared to gemcitabine and cisplatin (G/C) in a real-world clinical setting.

Approach:

• Study Design: Retrospective cohort study using deidentified electronic health record data from the TriNetX Global Collaborative Network.
• Patient Inclusion: Adults (age ≥18 years) diagnosed with mUC between September 2007 and September 2025 who initiated first-line systemic therapy with either EV/P or G/C.
• Outcome Measures: Primary outcome was OS; secondary outcomes included treatment sequencing patterns, time to next treatment (TTNT), early hospitalizations (EHA), and adverse events (AEs).
• Data Analysis: Cohort construction and exposure assignment were based on medication administration records. Adjustments were made for baseline demographics and comorbidities.

Key Findings:

• EV/P demonstrated superior overall survival compared to G/C in the retrospective cohort, with specific statistical measures to be detailed in the full study.
• Subgroup analyses indicated variations in OS based on age, race, sex, and other clinical characteristics, with specific data to be provided.
• Adverse events were documented and analyzed, focusing on treatment-related toxic effects, with detailed results available in the full study.

Interpretation:

Limitations:

• The study is retrospective and may be subject to biases inherent in observational data, which could affect the reliability of the findings.
• Generalizability may be limited due to the exclusion of patients with poor performance status or significant comorbidities in clinical trials, which may not reflect the broader mUC population.

Conclusion:

Observational data are essential to assess the effectiveness of EV/P in routine clinical practice for patients with mUC.