Dr Zhong on Upfront Dose Reductions of EV-Pembro in Advanced Urothelial Carcinoma

“[Most] patients who did get this upfront dose reduction were significantly older [than those who did not], [and] they typically had a worse performance status or [were] more anemic at baseline. Since a strong trend still persisted and given the degree of the inferior PFS and OS, early dose intensity does matter, [and] it warrants further investigation moving forward.”

Jeffrey Zhong, MD, a hematology/oncology fellow at Case Western Reserve University Hospitals, discussed findings from a study of upfront dose reductions on the efficacy of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) in advanced urothelial carcinoma.

Zhong and his coauthors retrospectively analyzed data from patients with advanced urothelial carcinoma who received enfortumab vedotin plus pembrolizumab from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) database.¹ UNITE is a multisite database that includes results from 17 academic centers in the United States. An upfront dose reduction was defined as a starting dose of 1.00 mg/kg or 0.75 mg/kg of enfortumab vedotin.

Findings from the study presented during the OncLive National Fellows Forum: Genitourinary Cancer prior to the 2026 Genitourinary Cancers Symposium, revealed that patients who received an upfront dose reduction (n = 94) experienced a median progression-free survival (PFS) of 5.1 months compared with 11.5 months among patients with no upfront dose reduction (n = 352; HR, 1.50; 95% CI, 1.11-2.02; P = .008), Zhong said. The median overall survival (OS) was 11.7 months and 21.6 months, respectively (HR, 1.56; 95% CI, 1.11-2.20; P = .01), he added. Data from a multivariable analysis that adjusted for age and other prognostic factors showed trend toward decreased PFS and OS outcomes was observed with upfront enfortumab vedotin dose reduction, but this was not statistically significant, he noted.

Patients who received an upfront dose reduction of enfortumab vedotin were often older, had a worse performance status, and were more anemic at baseline compared with those who did not, Zhong explained. He noted that the survival differences observed in the study could be partially reflective of the effects of baseline prognostic risk factors rather than the early dose intensity alone. However, further investigation into the effect of early dose intensity is warranted given these PFS and OS findings, he concluded.