Consistent PFS, OS Benefit With Enfortumab Vedotin Plus Pembrolizumab

In the phase 3 EV-302 study, progression-free survival (PFS) and overall survival (OS) improved with the first-line Nectin-4-directed antibody-drug conjugate enfortumab vedotin plus pembrolizumab (EV+P) compared with platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC), according to research presented at the European Society for Medical Oncology Congress 2024.

Researchers, led by Thomas B. Powles, MD, MBBS, also measured the impact of Nectin-4 expression on outcomes with first-line EV+P by immunohistochemistry (H-score).

Patients were randomly assigned 1:1 to receive EV 1.25 mg/kg intravenously (IV) on days one and eight every three weeks plus P 200 mg IV on day one every three weeks or to receive chemotherapy (gemcitabine plus cisplatin/carboplatin).

Nectin-4 expression was retrospectively assessed by immunohistochemistry (H-score) in tumor tissue. PFS and OS were assessed in Nectin-4 expression subgroups as well as in responders and nonresponders.

Nectin-4 expression was evaluable in 800 participants (EV+P, n=394; chemo, n=406). The median H-score was 280 and 270 in the EV+P and chemo arms, respectively; 38 and 50 patients had an H-score <150, respectively. In the H-score subgroups, Hazard ratio (HR) for PFS was 0.40 (95% CI, 0.32-0.50), 0.68 (95% CI, 0.41-1.13), and 0.54 (95% CI, 0.29-1.00), respectively. HR for OS was 0.47 (95% CI, 0.36-0.61), 0.44 (95% CI, 0.22-0.86), and 0.53 (95% CI, 0.27-1.05), respectively.

EV+P showed consistent PFS and OS benefit across subgroups regardless of Nectin-4 expression. Nectin-4 does not predict benefit from EV+P.