Enfortumab vedotin plus pembrolizumab in treatment-naïve metastatic urothelial carcinoma patients: An Austrian real-world analysis.

Antibody-drug conjugates (ADCs) and immunotherapy have changed the treatment landscape for locally advanced and metastatic urothelial carcinoma (la/mUC). Clinical trials have demonstrated the superiority of enfortumab vedotin (EV) combined with pembrolizumab (P) over chemotherapy. This retrospective, multicentre Austrian registry analysis evaluated the effectiveness and safety of EV + P in treatment-naïve la/mUC patients in a real-world setting. This study included 203 first-line EV + P treated patients from 20 Austrian centres. The majority were male (77.3%), with a median age of 70 years (range, 26-92), while 33.5% were ≥75 years. Comorbidities were common, with 25.1% having a Charlson Comorbidity Index (CCI) ≥ 5, and 46.3% moderate to severe renal impairment. Among 195 evaluable patients, the objective response rate (ORR) was 63.6% (95% CI, 56.6-70.0), including 21.5% complete responses and 42.1% partial responses. Disease control was achieved in 75.4% (95% CI, 68.9-80.9). Median progression-free survival (PFS) and overall survival (OS) were not reached after a median follow-up of 5.8 months. Poor outcomes were associated with ECOG PS >2 (PFS, p = .003; OS, p< .001) and CCI ≥5 (PFS, p = .011; OS, p = .08). EV + P was generally well tolerated; grade ≥3 treatment-related adverse events occurred in 38.4% of patients and immune-related adverse events in 19.2%. Limitations of this study include its retrospective design and short follow-up. These findings support the clinical use of EV + P as first-line treatment for la/mUC, demonstrating substantial effectiveness and manageable toxicity in a large real-world population, including elderly and comorbid patients. Extended follow-up is warranted to determine long-term survival and predictive markers of response.