A new study shows that a combination of enfortumab vedotin and pembrolizumab, given before and after surgery, may significantly improve survival for patients with muscle‑invasive bladder cancer who cannot receive the standard cisplatin-based chemotherapy.
Study overview
In this phase 3 clinical trial, 344 patients with muscle‑invasive bladder cancer who were not candidates for cisplatin (or chose not to receive it) were divided into two groups.
- One group received enfortumab vedotin and pembrolizumab both before and after surgery, along with standard surgical removal of the bladder (radical cystectomy) and pelvic lymph node dissection.
- The other group received surgery alone.
The main goal was to see how long patients lived without their cancer returning or progressing (called event‑free survival). Researchers also looked at overall survival, tumor response after surgery, and safety.
Key findings
After about 2 years of follow-up:
- Event‑free survival: 75% of patients in the combination‑therapy group were alive without cancer returning, compared with 39% in the surgery‑only group.
- Overall survival: 80% of patients who received the combination were alive at 2 years, versus 63% in the surgery group.
- Complete response: 57% of treated patients had no remaining cancer at the time of surgery, compared with 9% who had surgery alone.
While nearly all patients in the treatment group experienced some side effects, severe (grade 3 or higher) side effects occurred in about 71% of them. The most common issues were fatigue, rash, and nerve pain (neuropathy).
What this means for patients
For people with muscle‑invasive bladder cancer who cannot receive cisplatin, the combination of enfortumab vedotin and pembrolizumab around the time of surgery may offer a new, more effective treatment option. These promising results highlight ongoing progress in expanding treatment access and improving outcomes for this group of patients.
About Padcev (Enfortumab Vedotin)
Padcev is a novel precision cancer medicine known as an antibody drug conjugate, a type of therapy that combines an antibody that targets a specific protein on the surface of tumor cells with a payload of powerful chemotherapy. It is composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target which is expressed on many solid tumors. This antibody is chemically linked with an agent that penetrates the tumor cell and destroys its structure.
Padcev was initially approved by the U.S. Food and Drug Administration in December 2019 for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. The FDA expanded the approval to include Padcev in combination with Keytruda immunotherapy.
Reference:
Vulsteke C, Adra N, Danchaivijitr P, et al; KEYNOTE-905/EV-303 Investigators. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Feb 18. doi: 10.1056/NEJMoa2511674.
