Bladder Cancer Therapy Enfortumab Vedotin (Padcev®) Provides Lasting Benefits, Long-Term Data Confirms

This story was originally published in December 2025. It was updated on July 14, 2026.

A powerful treatment for bladder cancer provides lasting survival benefits, new follow-up data from clinical trials confirms. The therapy consists of a combination of two drugs — enfortumab vedotin (Padcev®) and an immunotherapy drug, pembrolizumab (Keytruda®).

Updated results from key clinical trials show that people receiving the drug combination (EV+P) lived twice as long as people receiving standard chemotherapy. In addition, the treatment has a lasting protective effect that was still evident after five years — both at preventing the cancer from returning and extending survival.

The new data helps cement EV+P as the preferred first-line treatment for urothelial carcinoma, the most common form of bladder cancer that has spread. 

“As an oncologist treating bladder cancer for more than two decades, this feels like a huge sea change and hopefully a turning point toward longer survival from this difficult disease,” says genitourinary oncologist and bladder cancer specialist Jonathan Rosenberg, MD. 

Dr. Rosenberg led multiple clinical trials testing EV alone or in combination with other medicines for bladder cancer. Combining enfortumab vedotin with pembrolizumab, a type of immunotherapy drug called a checkpoint inhibitor, has been especially effective. Results from those studies led the U.S. Food and Drug Administration (FDA) to approve the EV+P combination in 2023 for people newly diagnosed with metastatic urothelial carcinoma. 

New drug combination improves survival compared with chemotherapy

The traditional first-line treatment for bladder cancer that has spread had been platinum-based chemotherapy. The emergence of EV+P as an option has been a major advantage for all bladder cancer patients.

Follow-up data from two trials — EV-302/KEYNOTE-A39 and EV-103/KEYNOTE-869 — continue to show a striking benefit from the drug combination compared with standard platinum-based chemotherapy.

• Overall survival: 
  • At a follow-up of 3.5 years in the EV-302 trial, the combination achieved a median overall survival of 33.6 months, compared with 15.9 months in people receiving chemotherapy.
  • The estimated 5-year overall survival rate was 41.5% in the EV-103 trial, and no new treatment-related deaths were reported. 
• Depth and durability of response: 
  • In people receiving EV+P, the objective response rate (the percentage of people in whom the tumor shrank) was 73.3%. 
  • The estimated 5-year progression-free survival — the length of time a patient lives without the cancer coming back or getting worse — was 38.2%.

 

 

Antibody-drug conjugates deliver a precise payload to cancer cells

Enfortumab vedotin is a newer type of therapy called an antibody-drug conjugate. This type of drug works to treat cancer by combining three parts:

• An antibody that binds to specific proteins or receptors on the surface of the cancer cell.
• A drug, such as chemotherapy, that is toxic to the cancer cell.
• A linker that connects the drug and antibody, keeping the drug bound to the antibody and shielded from the body until it arrives at the cancer cell.

Targeting the nectin-4 protein in bladder cancer

On a search-and-destroy mission, enfortumab vedotin binds to a protein on cancer cells called nectin-4 and delivers a chemotherapy drug called monomethyl auristatin E. The antibody-drug conjugate selectively delivers monomethyl auristatin E to the cancer cells, killing them while sparing normal body parts from high doses of the drug.

Expanded approval in 2025

EV+P has become available to more bladder cancer patients in recent years. In November 2025, the FDA also approved the combination to be given before and after surgery for people with muscle-invasive urothelial carcinoma — the approval was based on the EV-303/KEYNOTE-905 trial, which showed treatment reduced the risk of death from cancer by half.

Many people with muscle-invasive bladder cancer that has not spread to other parts of the body (stage 2 and stage 3 bladder cancer) undergo bladder-removal surgery (radical cystectomy) as the main treatment. But historically, the cancer returns in about half the patients, requiring further treatment — many of these patients can’t receive the potent cisplatin-based chemotherapies that are standard after recurrence. 

The 2025 approval expanded the number of patients who could benefit from EV+P treatment because it included people with earlier-stage disease, dramatically improving outcomes compared with surgery alone, and in another trial compared with conventional chemotherapy with gemcitabine and cisplatin. 

The new results represent another step forward in establishing antibody-drug conjugates as a primary treatment option, even at earlier stages of bladder cancer.