The European Commission has approved enfortumab vedotin (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received platinum-containing chemotherapy and a PD-1/L1 inhibitor.1
The approval was based on data from the phase 3 EV-301 trial, in which enfortumab vedotin reduced the risk of death by 30% versus chemotherapy in patients with heavily pretreated locally advanced or metastatic urothelial carcinoma.2,3
“The EV-301 study is the first randomized trial to show improved overall survival in patients with advanced urothelial cancer who received a platinum-containing chemotherapy and an immunotherapy," Ignacio Durán, MD, PhD, Hospital Universitario Marqués de Valdecilla, Spain, stated in a press release. "This approval of enfortumab vedotin from the European Commission is an important moment for these patients and their physicians.
The open-label, randomized EV-301 trial (NCT03474107) included 608 patients with histologically or cytologically confirmed urothelial cancer, including patients with squamous differentiation or mixed cell types, were enrolled in the study and randomized 1:1 with stratification to either the enfortumab vedotin (n = 301) arm or the chemotherapy arm (n = 307).
Eligible patients had radiographic progression or relapsed during or after immune checkpoint inhibition for the treatment of advanced urothelial cancer and had received prior platinum-containing chemotherapy; patients also had an ECOG performance status of 0 or 1. Stratification variables included ECOG performance status (0 or 1), region of the world, and the presence or absence of liver metastasis.
The median overall survival (OS) with enfortumab vedotin was 12.88 months versus 8.97 months with chemotherapy, which translated to a 30% reduction in the risk of death (HR, 0.70; P = .00142). Subgroup analyses for OS favored the enfortumab vedotin arm for all groups excepts female patients (HR, 1.17).
Median progression-free survival (PFS) with enfortumab vedotin was 5.55 months versus 3.71 months with chemotherapy (HR, 0.62; P <.00001).
Confirmed ORR in the enfortumab vedotin arm was 40.6%, which included CRs in 4.9%, and the disease control rate (DCR) was 71.9%. In the chemotherapy arm, the ORR was 17.9% with CRs in 2.7%, and a DCR of 53.4% (P < .001).
Treatment-related adverse event (TRAE) rates were similar between the 2 arms, with any-TRAE rates of 94% in the investigational arm and 92% in the control arm, and grade ≥3 TRAE rates of 51% and 50%, respectively. Serious TRAEs were reported in 23% of patients in each arm and TRAEs led to treatment discontinuation in 14% of patients in the enfortumab vedotin arm and 11% in the chemotherapy arm.
1. European Commission Approves PADCEV™ (enfortumab vedotin) for Locally Advanced or Metastatic Urothelial Cancer. Published online April 13, 2022. Accessed April 13, 2022. https://prn.to/3JF0zZY
2. Powles T, Rosenberg JE, Sonpavde G, et al. Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 2021;39(suppl 6):393. doi:10.1200/JCO.2021.39.6_suppl.393
3. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. Published online February 12, 2021. N Engl J Med. doi:10.1056/NEJMoa2035807