The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of 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, according to Astellas Pharma and Seagen, the codevelopers of the antibody-drug conjugate.1
The CHMP based its opinion 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 European Commission will now review the opinion and make a final decision on approval. An approval would make enfortumab vedotin commercially available for this indication in the European Union, as well as Iceland, Norway, and Liechtenstein.
"People with advanced bladder cancer have few treatment options after platinum-based chemotherapy and immunotherapy," Ahsan Arozullah, MD, MPH, vice president, Medical Sciences-Oncology, Astellas, stated in a news release. "The CHMP's positive opinion is an important step as we work to expand availability of enfortumab vedotin as quickly as possible."
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. Astellas and Seagen Receive Positive CHMP Opinion for PADCEV™ (enfortumab vedotin) in Locally Advanced or Metastatic Urothelial Cancer. Published online December 17, 2021. Accessed December 17, 2021. https://bit.ly/3DZkVKE.
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