by Dr. C.H. Weaver M.D. updated 12/2019
There are currently no approved treatment options for patients with advanced bladder cancer after standard chemotherapy and immune treatments, but the results of a phase II clinical trial presented at the June 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago led to the U.S. Food and Drug Administration (FDA) granting Breakthrough Therapy Designation to enfortumab vedotin (EV) for patients with locally advanced or metastatic urothelial (bladder) cancer who were previously treated with checkpoint inhibitors (1) and now full FDA approval.
Enfortumab vedotin is a novel precision cancer medicine known as an antibody drug conjugate, a type of therapy that combines an antibody that targets a specific protein on the surface of tumor cells with a payload of powerful chemotherapy.
It is composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target which is expressed on many solid tumors. This antibody is chemically linked with an agent that penetrates the tumor cell and destroys its structure.
In the multi-institutional clinical trial reported at ASCO Padcev produced responses in 44% of patients with locally advanced or metastatic urothelial cancer who had been previously treated with chemotherapy and checkpoint inhibitors.
Among 125 patients who had received both standard chemotherapy plus a checkpoint inhibitor and Padcev, 12% had a complete response with no detectable sign of cancer and the median overall survival was 11.7 months. Notably, 38% of people whose cancer had spread to the liver responded to the treatment.
The most common side effects for patients taking Padcev were fatigue, peripheral neuropathy decreased appetite, rash, hair loss, nausea, altered taste, diarrhea, dry eye, itching and dry skin.
The U.S. Food and Drug Administration granted approval to Padcev for the treatment of adult patients with locally or metastatic urothelial cancer who have previously been treated with a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy. Urothelial cancer, accounting for more than 90% of bladder cancers, begins in cells that line the bladder and nearby organs. Padcev represents a new type of therapy for patients with advanced urothelial cancer whose disease has progressed on chemotherapy and immunotherapy.
Padcev is undergoing continued evaluation in comparative trials for FDA approval and being combined with other precision cancer medicines and immunotherapies like Keytruda in order to determine its optimal use.