New long term data confirms that a two drug combination for advanced bladder cancer more than doubles survival compared to standard chemotherapy, with benefits lasting at least five years. The findings solidify the regimen as a new standard of care for patients with metastatic urothelial carcinoma, the most common form of the disease.
Updated results from the EV-302/KEYNOTE-A39 and EV-103/KEYNOTE-869 trials show that patients receiving enfortumab vedotin (Padcev) plus the immunotherapy pembrolizumab (Keytruda) lived twice as long as those given platinum based chemotherapy. The protective effect remained evident after five years, both in preventing cancer recurrence and extending overall survival. The U.S. Food and Drug Administration first approved this combination in 2023 for newly diagnosed metastatic disease.
Enfortumab vedotin belongs to a class of drugs called antibody drug conjugates. It works like a guided missile: it binds to a protein called nectin-4 found on cancer cells and delivers a chemotherapy agent called monomethyl auristatin E directly into the tumor. This targeted approach kills cancer cells while sparing healthy tissue from high doses of toxic drugs. The addition of pembrolizumab, a checkpoint inhibitor, helps the immune system recognize and attack the cancer more effectively.
Expanded Access for Earlier Stage Disease
In November 2025, the FDA broadened the approval of EV+P to include patients with muscle invasive urothelial carcinoma that has not yet spread. These patients, with stage 2 or stage 3 bladder cancer, typically undergo bladder removal surgery. Historically, the cancer returns in about half of these patients, and many cannot tolerate the standard cisplatin based chemotherapy given after recurrence. The new approval allows the drug combination to be given before and after surgery, based on the EV-303/KEYNOTE-905 trial, which showed the treatment reduced the risk of death from cancer by half.
The expanded indication dramatically improves outcomes compared with surgery alone or conventional chemotherapy with gemcitabine and cisplatin. Researchers say the results represent a major step in establishing antibody drug conjugates as a primary treatment option even at earlier stages of bladder cancer. For patients who have faced a historically difficult disease with limited options, these advances offer a meaningful chance at longer survival and better quality of life.