FDA

Keytruda plus Padcev OK’d for muscle-invasive bladder cancer

November 28, 2025

On November 21, 2025, FDA approved Keytruda (pembrolizumab) or Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) with Padcev (enfortumab vedotin-ejfv) as neoadjuvant treatment followed by adjuvant treatment after cystectomy for adults with muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin.

Efficacy

Efficacy was evaluated in the open-label, randomized, multicenter, active-controlled KEYNOTE-905/EV-303 trial (NCT03924895) involving 344 patients with previously untreated MIBC who were candidates for radical cystectomy (RC) with pelvic lymph node dissection (PLND) but were ineligible for or declined cisplatin-based chemotherapy. Patients were randomized (1:1) to receive neoadjuvant pembrolizumab and enfortumab vedotin-ejfv followed by surgery followed by adjuvant enfortumab vedotin-ejfv in combination with pembrolizumab followed by pembrolizumab as a single agent or to undergo immediate surgery alone.

The major efficacy outcome measure was event-free survival (EFS) assessed by blinded independent central review. Overall survival (OS) was an additional efficacy outcome. The trial demonstrated statistically significant improvements in EFS and OS in patients treated with pembrolizumab and enfortumab vedotin-ejfv before and after RC and PLND compared with surgery alone. Median EFS wasn’t reached (NR) (95% confidence interval [CI], 37.3, NR) in the pembrolizumab and enfortumab vedotin arm and was 15.7 months (95% CI, 10.3-20.5) in the RC and PLND arm (hazard ratio [HR], 0.40; 95% CI, 0.28-0.57; p-value <0.0001). Median OS was NR (95% CI, NR, NR) and 41.7 months (95% CI, 31.8, NR) in the respective arms (HR, 0.50; 95% CI, 0.33-0.74; p-value 0.0002).

Safety

The overall safety profile of enfortumab vedotin-ejfv with pembrolizumab in KEYNOTE-905/EV-303 was similar to that observed in prior trials in advanced urothelial cancer. The pembrolizumab prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. The enfortumab vedotin-ejfv prescribing information includes warnings and precautions for skin reactions, hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, ocular disorders, infusion site extravasation, and embryo-fetal toxicity.

Sources:

FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer

Keytruda (pembrolizumab) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125514s188lbl.pdf Revised November 2025. Accessed November 26, 2025.

Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761467s001lbl.pdf Revised November 2025. Accessed November 26, 2025.

Padcev (enfortumab vedotin-ejfv) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761137s032lbl.pdf Revised November 2025. Accessed November 26, 2025.