The immune checkpoint inhibitor Keytruda (pembrolizumab) plus the antibody-drug conjugate Padcev (enfortumab vedotin) improved overall survival for previously untreated people with inoperable urothelial carcinoma, which usually involves the bladder.

The Phase III KEYNOTE-A39 trial evaluated Keytruda plus Padcev, a monoclonal antibody that delivers a potent chemotherapy drug directly to tumors, versus platinum-based chemotherapy as first-line treatment for people with locally advanced or metastatic urothelial cancer.

Progression-free survival—meaning patients were still alive without worsening disease—was twice as long with the Keytruda-Padcev combination compared with chemotherapy (12.5 versus 6.3 months). Likewise, overall survival was 31.5 months with the combination versus 16.1 months with chemotherapy, representing a 53% reduction in the risk of death. The complete response rate, indicating full tumor regression, was 29% in the Keytruda-Padcev arm versus 13% in the chemotherapy arm. The median duration of response was seven months in the chemotherapy arm but was not reached in the Keytruda-Padcev arm because a majority of patients were still responding. Treatment was generally safe, but side effects were common; 56% in the Keytruda-Padcev group and 70% in the chemotherapy group experienced severe treatment-related adverse events.

“We’ve never beaten chemotherapy” for overall survival in the first-line setting, said Thomas Powles, MD, of Barts Cancer Centre at Queen Mary University of London, whose presentation earned a standing ovation. These results, he added, “open a new chapter” for these patients, who face an urgent need for new therapies.