FDA Approves AstraZeneca's Imfinzi With Enfortumab Vedotin for Cisplatin-Ineligible Bladder Cancer

The U.S. Food and Drug Administration on Nov. 13 approved AstraZeneca's Imfinzi (durvalumab) in combination with enfortumab vedotin for adults with muscle-invasive bladder cancer who cannot receive, or have refused, cisplatin-based chemotherapy. The regimen pairs the two drugs before surgery to remove the bladder and continues Imfinzi alone afterward, giving a group of patients that has historically relied on surgery alone a second immunotherapy-based perioperative option in the United States.

Disease and treatment background

Muscle-invasive bladder cancer is cancer that has grown into the muscle wall of the bladder. AstraZeneca estimates that about 16,000 people in the United States will be treated for the disease in 2026, and that roughly one in four bladder cancer patients has muscle-invasive disease. Standard care for fit patients has long been cisplatin-based chemotherapy before radical cystectomy. The company said up to half of patients cannot take cisplatin, often because of reduced kidney function or other health conditions, and that about half of patients treated with surgery alone see their cancer return.

The approved schedule calls for three three-week cycles of Imfinzi 1,500 mg plus enfortumab vedotin 1.25 mg/kg before surgery, then up to nine four-week cycles of Imfinzi after cystectomy, according to the FDA. Patients under 30 kg receive weight-based Imfinzi dosing. Enfortumab vedotin is an antibody-drug conjugate sold as Padcev by Pfizer and Astellas, and Imfinzi is a PD-L1 inhibitor.

In VOLGA, median event-free survival was not reached for the combination versus 12.1 months for surgery alone, and two-year event-free survival was 64% versus 45%. Median overall survival was not reached in either arm, with two-year survival of 78% versus 69%. Grade 3 or 4 adverse events of any cause occurred in 64% of patients on the combination and 44% in the comparator arm. The FDA listed liver enzyme increases, low hemoglobin, rash, itching, fatigue, diarrhea, nausea, peripheral neuropathy and hair loss among the most common reactions.

Industry implications

The approval extends a shift in how early-stage bladder cancer is treated: moving immunotherapy and antibody-drug conjugates out of the metastatic setting and into the curative window around surgery. In March 2025, Imfinzi became the first immunotherapy cleared for perioperative use in this disease, based on the NIAGARA trial, but that regimen includes cisplatin and therefore excludes patients who cannot tolerate it. VOLGA fills that gap for AstraZeneca and gives the drug a role across cisplatin-eligible, cisplatin-ineligible and non-muscle-invasive disease.

The design is also notable. Enfortumab vedotin is given only before surgery in VOLGA, while the competing Merck and Pfizer regimen continues both drugs after cystectomy. That difference affects the number of infusions, the cumulative exposure to an antibody-drug conjugate known for skin and nerve toxicities, and the planning burden for urology and oncology teams. Physicians will weigh those trade-offs alongside the trial data, since no head-to-head study compares the two approaches.

Competitive and supply chain implications

The FDA cleared Padcev plus Keytruda for cisplatin-ineligible muscle-invasive disease in November 2025, and in July 2026 broadened that label to cover patients regardless of cisplatin eligibility, based on the EV-304 trial. AstraZeneca now enters a setting where a competing perioperative regimen has a head start of about a year. Both regimens depend on the same antibody-drug conjugate, which means Pfizer and Astellas supply the backbone drug for both their own regimen and AstraZeneca's.

For manufacturers and health systems, the result is higher demand for enfortumab vedotin in the neoadjuvant setting and more infusion-center capacity tied to pre-surgical treatment. Imfinzi's fixed dosing and every-four-week adjuvant schedule may simplify logistics after surgery. Payers will see two branded checkpoint inhibitors competing for the same patients, with formulary positioning likely to follow guideline committee reviews.

Regional implications

In the United States, the decision is immediately relevant for academic cancer centers and community urology practices that manage older patients with kidney impairment, the group most likely to be cisplatin-ineligible. Use of Project Orbis means regulators in Australia, Brazil, Canada, Israel, Singapore and the U.K. reviewed the file at the same time, which could shorten the gap before approvals in those markets.

Europe and Japan remain under review. NIAGARA-based approvals for cisplatin-eligible patients already exist in more than 50 countries, according to AstraZeneca, so prescribers in those regions are familiar with perioperative Imfinzi. Decisions on VOLGA in the EU and Japan will determine whether AstraZeneca can offer a cisplatin-free perioperative option outside the U.S. on a similar timeline to its rivals.

What comes next

• The full prescribing information is expected to be posted on Drugs@FDA, according to the agency.
• Regulatory decisions on the VOLGA regimen are pending in the European Union, Japan and other countries.
• Project Orbis partners in Australia, Brazil, Canada, Israel, Singapore and the U.K. are expected to complete their concurrent reviews.
• Further VOLGA readouts, including pathologic complete response, disease-free survival and data from the trial's Imjudo triplet arm, are secondary endpoints that may be reported later.
• Clinical guideline committees will need to assess where the VOLGA regimen fits alongside Padcev plus Keytruda.

Sources

• U.S. FDA: FDA approves durvalumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer
• AstraZeneca: Perioperative Imfinzi approved in the US with neoadjuvant enfortumab vedotin
• Fierce Pharma: Padcev-Keytruda combo expands bladder cancer reach with FDA approval
• BioPharm International: FDA approves Padcev plus Keytruda for muscle-invasive bladder cancer

Image: AstraZeneca building in Cambridge, U.K., by D Wells via Wikimedia Commons, CC BY-SA 4.0. Cropped and edited by Credence Research.