FDA approved Imfinzi plus Padcev before surgery for cisplatin ineligible bladder cancer on Nov. 13, 2026, as VOLGA showed an EFS hazard ratio of 0.51.
Last updated: November 14, 2026
Quick answer: On November 13, 2026, the FDA approved AstraZeneca’s durvalumab (Imfinzi) with enfortumab vedotin (Padcev) before radical cystectomy, then durvalumab alone after surgery, for adults with muscle invasive bladder cancer who cannot take or refuse cisplatin. In the VOLGA trial, event free survival improved with a hazard ratio of 0.51 versus surgery alone.
Scope: what the FDA approved, what VOLGA showed, how the regimen differs from Merck’s Keytruda plus Padcev, and what it means for urology and oncology teams. All trial figures come from FDA approval notices unless attributed.
What did the FDA approve on November 13, 2026?
The FDA approved durvalumab in combination with enfortumab vedotin-ejfv as neoadjuvant treatment, followed by single agent durvalumab as adjuvant treatment after radical cystectomy, for adults with muscle invasive bladder cancer (MIBC) who are ineligible for or who have refused cisplatin based chemotherapy. That is the exact indication language on the FDA notice.
Durvalumab is a PD-L1 blocking antibody. Enfortumab vedotin is an antibody drug conjugate aimed at Nectin-4. The FDA reviewed the application under priority review and acted six weeks ahead of its goal date, according to the agency’s notice. It was reviewed through Project Orbis with Australia’s TGA, Brazil’s ANVISA, Health Canada, Israel’s Ministry of Health, Singapore’s HSA and the UK’s MHRA, and the sponsor used FDA’s Assessment Aid.
The wording matters for practice. “Ineligible for or who have refused” cisplatin is broader than a strict medical ineligibility label, so patients who decline cisplatin are explicitly covered.
What did the VOLGA trial show?
VOLGA (NCT04960709) met its primary endpoint. Event free survival by blinded independent central review had a hazard ratio of 0.51 (95% CI 0.38 to 0.67, two sided p<0.0001) for durvalumab plus enfortumab vedotin versus radical cystectomy alone. Overall survival also improved, with a hazard ratio of 0.58.
VOLGA was a randomized, open label trial in 695 patients with MIBC who were candidates for radical cystectomy and were ineligible for or refused cisplatin. Patients were randomized 1:1:1 to the approved regimen, radical cystectomy alone, or a third investigational combination. OncLive, citing AstraZeneca, described that third arm as durvalumab, enfortumab vedotin and tremelimumab (Imjudo). Fierce Pharma reported in May that the triplet arm’s overall survival did not reach statistical significance at the interim analysis. The FDA notice reports no results for the third arm.
| VOLGA endpoint (FDA notice) | Imfinzi + Padcev, then Imfinzi | Radical cystectomy alone |
|---|---|---|
| Median event free survival | Not reached (95% CI 33.2 to not reached) | 12.1 months (95% CI 7.6 to 27.0) |
| EFS hazard ratio | 0.51 (95% CI 0.38 to 0.67), p<0.0001 | |
| Median overall survival | Not reached | Not reached |
| OS hazard ratio | 0.58 (95% CI 0.40 to 0.83), p=0.0027 | |
The FDA notice does not report pathologic complete response rates or median follow up. Those will matter to urologists and should come with the full presentation, which AstraZeneca said would happen at a medical meeting.
How is the regimen dosed?
Before surgery, patients weighing 30 kg or more get durvalumab 1,500 mg every 3 weeks plus enfortumab vedotin 1.25 mg/kg on Days 1 and 8, for 3 cycles. After cystectomy, durvalumab 1,500 mg runs every 4 weeks as a single agent for up to 9 cycles. Patients under 30 kg get weight based durvalumab at 20 mg/kg.
The operational point is that enfortumab vedotin is given only before surgery. AstraZeneca’s Susan Galbraith said in September, per OncLive, that this would be the first perioperative regimen with enfortumab vedotin given only before surgery. After cystectomy the patient is on a single PD-L1 antibody once a month.
The FDA lists more than 20 common adverse reactions, led by increased AST, increased ALT, decreased hemoglobin, rash, increased creatinine and pruritus. Warnings follow the durvalumab label: immune mediated adverse reactions, infusion related reactions, complications of allogeneic stem cell transplant and embryo fetal toxicity.
How does Imfinzi plus Padcev compare with Keytruda plus Padcev?
Both regimens now carry FDA approval for cisplatin ineligible MIBC, and they differ mainly in how long enfortumab vedotin runs. Merck’s pembrolizumab (Keytruda) plus enfortumab vedotin was approved in this setting on November 21, 2025, based on KEYNOTE-905/EV-303, and continues enfortumab vedotin after surgery.
| Feature (FDA notices) | Imfinzi + Padcev (VOLGA) | Keytruda + Padcev (KEYNOTE-905/EV-303) |
|---|---|---|
| FDA approval date | Nov 13, 2026 | Nov 21, 2025 |
| Patients randomized | 695 (three arms) | 344 (two arms) |
| Comparator | Radical cystectomy alone | Surgery alone (RC with PLND) |
| EFS hazard ratio | 0.51 (0.38 to 0.67) | 0.40 (0.28 to 0.57) |
| OS hazard ratio | 0.58 (0.40 to 0.83) | 0.50 (0.33 to 0.74) |
| Control arm median EFS | 12.1 months | 15.7 months |
| Padcev cycles | 3, all before surgery | 3 before plus 6 after surgery |
| Checkpoint inhibitor after surgery | Durvalumab every 4 weeks, up to 9 cycles | Pembrolizumab 200 mg every 3 weeks for 14 cycles or 400 mg every 6 weeks for 7 |
Do not read the hazard ratios as a head to head result. The trials enrolled different numbers of patients, had different designs and control arms, and no trial has compared the two regimens directly. What the table does show is a real choice in treatment burden: six fewer enfortumab vedotin cycles with the AstraZeneca regimen, against a longer track record and a broader label for the Merck regimen.
Where does this leave the MIBC market?
Merck’s regimen covers every cystectomy candidate, while AstraZeneca now covers the same population with two different regimens. On July 10, 2026, the FDA extended Keytruda plus enfortumab vedotin to all MIBC patients who are candidates for cystectomy, based on KEYNOTE-B15/EV-304 in 808 cisplatin eligible patients (EFS HR 0.53, OS HR 0.65 versus gemcitabine and cisplatin).
| Setting | AstraZeneca option | Merck option |
|---|---|---|
| Cisplatin eligible | Imfinzi + gemcitabine/cisplatin (NIAGARA, approved Mar 28, 2025; EFS HR 0.68, OS HR 0.75) | Keytruda + Padcev (KEYNOTE-B15/EV-304, approved Jul 10, 2026) |
| Cisplatin ineligible or refusing | Imfinzi + Padcev (VOLGA, approved Nov 13, 2026) | Keytruda + Padcev (KEYNOTE-905/EV-303, approved Nov 21, 2025) |
For pharma strategy, that split matters. Merck can offer one regimen across the whole cystectomy population. AstraZeneca offers a chemotherapy backbone where cisplatin works and a shorter enfortumab vedotin exposure where it does not. Enfortumab vedotin sits in every one of these immunotherapy plus ADC options, which makes Padcev (Astellas, per the FDA notice) the common thread in perioperative bladder cancer.
The size of the population is why this fight matters. Thomas Powles of Barts Cancer Centre, quoted by OncLive and Fierce Pharma from AstraZeneca’s May release, said up to half of MIBC patients are not eligible for cisplatin.
What should treatment teams do now? (our framework)
This is our checklist for urology, oncology and pharmacy teams, not FDA guidance.
- Document cisplatin status precisely. The label covers patients ineligible for or refusing cisplatin; record which applies.
- Compare treatment burden with the patient. Three enfortumab vedotin cycles before surgery versus nine total; monthly versus every three or six week checkpoint dosing after surgery.
- Plan surgery timing around 3 neoadjuvant cycles of 3 weeks each, so about 9 weeks before cystectomy (our arithmetic).
- Update order sets and formulary entries for both perioperative regimens, including weight based durvalumab for patients under 30 kg.
- Brief nursing on toxicity monitoring for liver enzymes, rash and pruritus during the neoadjuvant phase, plus immune mediated effects through adjuvant therapy.
- Watch payer policies. Expect plans to set criteria for choosing between two approved regimens in the same population.
- Track the full VOLGA data for pCR, follow up length and the triplet arm before building pathways.
What to watch next
- Full VOLGA results at a medical meeting, including pCR rates and the tremelimumab triplet arm.
- Decisions from the six Project Orbis partners named on the FDA notice.
- EU and Japan reviews, which OncLive reported were under way.
- NCCN guideline placement of both perioperative regimens.
- Any head to head or real world data comparing short and long enfortumab vedotin courses.
FAQ
What is the new Imfinzi bladder cancer approval?
On November 13, 2026, the FDA approved durvalumab (Imfinzi) with enfortumab vedotin (Padcev) before radical cystectomy, then durvalumab alone after surgery, for adults with muscle invasive bladder cancer who are ineligible for or refuse cisplatin.
What trial supported the approval?
VOLGA (NCT04960709), a randomized open label trial of 695 cisplatin ineligible or refusing MIBC patients who were cystectomy candidates.
How much did VOLGA improve event free survival?
The EFS hazard ratio was 0.51 (95% CI 0.38 to 0.67) versus surgery alone. Median EFS was not reached with the combination versus 12.1 months with surgery alone.
Did VOLGA improve overall survival?
Yes. The overall survival hazard ratio was 0.58 (95% CI 0.40 to 0.83, p=0.0027). Median OS was not reached in either arm.
How many cycles of Padcev does the Imfinzi regimen use?
Three cycles, all before surgery, with doses on Days 1 and 8 of each cycle. After surgery, only durvalumab continues.
How is it different from Keytruda plus Padcev?
Keytruda plus Padcev gives three Padcev cycles before surgery and six after, with pembrolizumab continuing for up to 42 weeks after surgery. The Imfinzi regimen stops Padcev at surgery.
Is Imfinzi plus Padcev better than Keytruda plus Padcev?
No trial has compared them directly. Their hazard ratios come from different trials with different designs and control arms, so they cannot be ranked from published data.
Who qualifies for the new regimen?
Adults with muscle invasive bladder cancer who are candidates for radical cystectomy and are ineligible for or have refused cisplatin based chemotherapy.
Did the FDA use priority review?
Yes. The FDA notice says the application had priority review and was approved six weeks ahead of the goal date.
What is Project Orbis in this approval?
Project Orbis is FDA’s program for concurrent cancer drug reviews with partner regulators. For this approval the partners were the TGA, ANVISA, Health Canada, Israel’s Ministry of Health, Singapore’s HSA and the MHRA.
What are the most common side effects?
The FDA notice lists increased AST and ALT, decreased hemoglobin, rash, increased creatinine and pruritus among the most common adverse reactions, along with immune mediated reactions as a warning.
Sources
- FDA, “FDA approves durvalumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer,” November 13, 2026 (primary).
- FDA, “FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer,” November 21, 2025 (primary).
- FDA, approval notice for pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for MIBC, July 10, 2026 (primary).
- FDA, “FDA approves durvalumab for muscle invasive bladder cancer” (NIAGARA), March 28, 2025 (primary).
- OncLive, priority review report, September 25, 2026 (attributed: VOLGA third arm, Galbraith and Powles quotes, EU and Japan reviews).
- Fierce Pharma, VOLGA interim results report, May 2026 (attributed: triplet arm OS, Powles quote).
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