FDA Approves Durvalumab Plus Enfortumab Vedotin for Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer

Clinical Summary:

• Regulatory Update: On November 13, 2026, the FDA approved durvalumab plus enfortumab vedotin as neoadjuvant treatment, followed by adjuvant durvalumab monotherapy following radical cystectomy, for patients with muscle-invasive bladder cancer who are ineligible for or have refused cisplatin-based chemotherapy. 
• Key Outcomes: This approval was based on results from the phase 3 VOLGA trial, which demonstrated significant improvements in event-free and overall survival with the durvalumab-based perioperative regimen compared with radical cystectomy alone, reducing the risk of an event-free survival event by 49% and the risk of death by 42%. 
• Clinical Relevance: This approval introduces a perioperative treatment option combining PD-L1 inhibition with antibody-drug conjugate therapy for cisplatin-ineligible patients with muscle-invasive bladder cancer, expanding treatment options beyond radical cystectomy alone. 

On November 13, 2026, the US Food and Drug Administration (FDA) approved durvalumab (Imfinzi; AstraZeneca) in combination with enfortumab vedotin (Padcev; Astellas Pharma and Pfizer) as neoadjuvant treatment, followed by durvalumab monotherapy following radical cystectomy, for patients with muscle-invasive bladder cancer who are ineligible for or have refused cisplatin-based chemotherapy, introducing a perioperative treatment option in this setting. 

This approval was based on results from the open-label, phase 3 VOLGA trial which enrolled 695 patients who were candidates for radical cystectomy and were either ineligible for or had declined cisplatin-based chemotherapy. Patients were randomized 1:1:1 to receive either neoadjuvant durvalumab plus enfortumab vedotin followed by radical cystectomy and adjuvant durvalumab, radical cystectomy alone, or an additional investigational combination regimen.

The primary efficacy end point was event-free survival (EFS), as assessed via blinded independent central review. Key secondary end points included overall survival (OS) and safety. 

At analysis, median EFS was not reached in the durvalumab plus enfortumab vedotin arm and was 12.1 months in the radical cystectomy arm, reducing the risk of an EFS event by 49% (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.38 to 0.67; two-sided P < .0001). 

Median OS was not reached in either treatment arm. However, the durvalumab-based regimen reduced the risk of death by 42% compared with radical cystectomy alone (HR, 0.58; 95% CI, 0.40 to 0.83; P = .0027).

The most common adverse reactions and laboratory abnormalities occurring in more than 20% of patients receiving durvalumab plus enfortumab vedotin included increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, rash, increased creatinine, pruritus, decreased calcium, increased lipase, increased potassium, urinary tract infection, increased amylase, fatigue, decreased sodium, decreased lymphocytes, diarrhea, decreased leukocytes, constipation, decreased appetite, increased alkaline phosphatase, dysgeusia, nausea, peripheral neuropathy, musculoskeletal pain, and alopecia.

For patients weighing at least 30 kg, the recommended neoadjuvant regimen consists of 1500 mg of durvalumab administered intravenously every 3 weeks in combination with 1.25 mg/kg of enfortumab vedotin on days 1 and 8 of each cycle for 3 cycles prior to surgery. 

Following radical cystectomy, patients will receive 1500 mg of durvalumab intravenously every 4 weeks for up to 9 cycles. 

For patients weighing less than 30 kg, the recommended dose of durvalumab is 20 mg/kg every 3 weeks during neoadjuvant treatment and 20 mg/kg every 4 weeks during adjuvant treatment, with enfortumab vedotin administered at 1.25 mg/kg on days 1 and 8 of each neoadjuvant cycle. 

Treatment should continue until disease progression that precludes definitive surgery, disease recurrence, unacceptable toxicity, or completion of the maximum 9 postoperative cycles.

The durvalumab 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.

This FDA approval expands perioperative treatment options for patients with muscle-invasive bladder cancer who are not receiving cisplatin-based chemotherapy, supported by significant improvements in EFS and OS with durvalumab plus enfortumab vedotin followed by adjuvant durvalumab compared with radical cystectomy alone.

Source:

US Food and Drug Administration. FDA approves durvalumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. Accessed on: November 13, 2026. https://www.fda.gov/drugs/cancer-approvals/fda-approves-durvalumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer