FDA approves enfortumab for locally advanced or metastatic urothelial Ca

Olivier Le Moal - stock.adobe.com

The FDA has granted accelerated approval to enfortumab vedotin-ejfv (PADCEV) for the treatment of adults with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before or after surgery or in a locally advanced or metastatic setting.

Enfortumab is the first FDA-approved treatment for these patients, according to a statement from Astellas and Seattle Genetics. It is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.

Enfortumab was evaluated in EV-201, a single-arm phase II multicenter trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy. The primary endpoint of confirmed objective response rate was 44% per blinded independent central review (55/125; 95% CI: 35.1, 53.2). Among patients treated with the single agent enfortumab, 12% experienced a complete response and 32% experienced a partial response. Median duration of response, a secondary endpoint, was 7.6 months (95% CI: 6.3, not estimable).

The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). The most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%), and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%), and fatigue (6%).

“Metastatic urothelial cancer is an aggressive and devastating disease with limited treatment options, and the approval of PADCEV is a significant advance for these patients who previously had limited options after initial therapies failed,” said Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, New York. “The PADCEV clinical trial enrolled a range of patients whose cancer was difficult to treat, including those whose disease had spread to the liver.”