On December 18, 2019, the FDA accelerated the approval of enfortumab vedotin-ejfv (Padcev; Astellas Pharma), a Nectin-4–directed antibody and microtubule inhibitor conjugate, for the treatment of adults with locally advanced or metastatic urothelial cancer after immunotherapy with a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy. These are the current standard treatments for patients with bladder cancer, the sixth most common cancer in the United States. Urothelial cancer accounts for >90% of bladder cancers.
Enfortumab vedotin-ejfv represents a new type of therapy for patients with advanced urothelial cancer whose disease progressed during chemotherapy and immunotherapy. The FDA granted a breakthrough therapy designation to this therapy.
“Antibody-drug conjugates are strategic tools in the targeted treatment of cancer. These conjugates combine the ability of monoclonal antibodies to target specific receptors on cancer cells and then deliver a drug to the cancer cell,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Padcev is an antibody-drug conjugate that targets Nectin-4, a cell surface protein expressed on bladder cancer cells and a cell-killing agent, monomethyl auristatin E.”
Enfortumab vedotin-ejfv was approved based on the results of a clinical trial of 125 patients with locally advanced or metastatic urothelial cancer who have received a PD-1 or PD-L1 inhibitor therapy and platinum-based chemotherapy.
The overall response rate was 44%, including 12% complete responses and 32% partial responses. The median duration of response to therapy with enfortumab vedotin-ejfv was 7.6 months.
The most common adverse events with enfortumab vedotin-ejfv were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, altered taste, diarrhea, dry eye, pruritis, and dry skin. Patients receiving this drug may have hyperglycemia, regardless of the presence of diabetes, as well as eye disorders, and the drug may cause harm to a fetus.