Real‑World Data on Urothelial Carcinoma Treatment

Investigators reported real-world safety and early activity of first-line enfortumab vedotin plus pembrolizumab, administered with routine intravenous dexamethasone premedication, in a Japanese multicenter retrospective cohort of patients with metastatic or unresectable urothelial carcinoma.

The analysis included 77 consecutive patients treated across five institutions, with a median age of 75 years at treatment initiation. Tumor response was assessable in 74 patients.

The authors described an objective response rate of 73.0% based on 54 objective responses (13 complete responses and 41 partial responses) and a disease control rate of 87.8% with stable disease documented in 11 patients.

Time-to-event outcomes were reported at a median follow-up of 6.7 months using Kaplan–Meier estimation. The investigators reported a 6-month progression-free survival estimate of 73.9% (95% CI, 60.8–83.2) and a 6-month overall survival estimate of 78.7% (95% CI, 65.9–87.2).

Cutaneous toxicity was reported as the most frequent treatment-related adverse event. Rash occurred in 52.0% of patients, and grade ≥3 skin reactions were reported in 3.9%. The median time to rash onset was 0.7 months (range, 0.1–6.9). For management of cutaneous toxicity, the investigators reported that systemic corticosteroids were required in 2 patients (2.6%), distinguishing this use from corticosteroids administered for other toxicities. The authors characterized skin events as common, typically early in onset, and infrequently high grade in this cohort.

Pulmonary toxicity was also described, with interstitial lung disease (ILD) reported in 16.9% of patients, including grade ≥3 ILD in 10.4%; investigators reported systemic corticosteroid therapy for ILD in 11 of the affected patients. The authors also detailed a routine supportive-care approach using intravenous dexamethasone premedication at 6.6 mg prior to each enfortumab vedotin infusion, and summarized cumulative exposure through early cycles as a median of six administrations (approximately 40 mg through cycle 3).

Treatment delivery during cycles 1–3 was described as starting at the standard enfortumab vedotin dose in most patients, with a subset experiencing dose reductions, day-8 omissions, or treatment delays.