New Targeted Therapy Regimen for Bladder Cancer 

A targeted therapy is now available for more patients with advanced bladder cancers  

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial carcinoma who cannot be treated with certain chemotherapies.  

Enfortumab vedotin-ejfv was previously approved as a monotherapy to treat locally advanced or metastatic urothelial carcinoma in patients who had already received one or more prior lines of treatment. The latest approval expands its use to patients who have not received prior treatment. 

Enfortumab vedotin-ejfv is a type of targeted therapy known as an antibody-drug conjugate that uses an antibody to selectively deliver a chemotherapy drug to cancer cells. The antibody of enfortumab vedotin-ejfv recognizes the nectin-4 protein, which is found on the surface of most bladder cancer cells. Pembrolizumab is a type of immunotherapy that releases the “brakes” on the immune system, allowing it to respond better to cancers. 

The accelerated approval is based on results from the EV-103/KEYNOTE-869 phase I/II multi-cohort clinical trial, in which 121 patients across three treatment cohorts received enfortumab vedotin-ejfv in combination with pembrolizumab. Patients were ineligible for cisplatin-containing chemotherapy and had not received prior systemic therapy to treat their locally advanced or metastatic urothelial cancers.  

Sixty-eight percent of patients had an objective response, including 12% who had complete responses. The median duration of response was 22 months among patients in two of the cohorts and was not reached among patients assigned to the other cohort.  

Urothelial carcinoma is the most common type of bladder cancer. According to federal statistics, it was estimated that 82,290 individuals would be diagnosed with bladder cancer and 16,710 patients would die of the disease in the U.S. in 2023. 

The FDA rendered its decision on April 3, 2023. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.