Durvalumab + Enfortumab Vedotin for Bladder Cancer
- A large study called VOLGA tested a new plan for people whose bladder cancer has grown into the bladder muscle (muscle-invasive bladder cancer) and who can’t have, or don’t want, the chemotherapy drug cisplatin.
- People who got two drugs, durvalumab and enfortumab vedotin, before surgery were less likely to have their cancer come back or get worse than people who had surgery alone. Most of them were alive two years later.
- For almost half of the people who got the combination therapy, no cancer was found in the bladder when it was removed.
- This combination is not approved for use in the U.S. yet, but the Food and Drug Administration (FDA) has given it “priority review” status, and a decision is expected by the end of 2026.
The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, one of the world’s biggest cancer conferences.
Read MoreThe durvalumab and enfortumab vedotin combination offers a much-needed alternative for this patient population.
What to Know About the Drug Combination
Muscle-invasive bladder cancer, or MIBC, is bladder cancer that has grown past the inner lining of the bladder and into the thick muscle wall. It hasn’t spread to distant parts of the body, so doctors treat it with the goal of a cure.
The main treatment is usually surgery called radical cystectomy, where the whole bladder and sometimes nearby lymph nodes and organs are removed. Even after surgery, the cancer can come back. That’s why doctors look for treatments to give before or after surgery to lower that risk.
VOLGA is a large, phase 3 trial, which means a trial that evaluates a new treatment against the current standard. VOLGA tested whether durvalumab and enfortumab vedotin could be an effective alternative to cisplatin for these patients. Both approaches attempt to rid the body of any cancer that could remain in the body after surgery.
Dr. Alexandra Drakaki explains why the VOLGA trial results are important.
“Getting treatment before the surgery, what we are doing is we are cleaning the body of potential microscopic disease that we don’t even see,” Dr. Bellmunt explains.
Durvalumab (brand name Imfinzi) is a type of immunotherapy drug called an immune checkpoint inhibitor. Cancer cells can put “brakes” on your immune system so it leaves them alone. Checkpoint inhibitors release those brakes so your immune cells can attack the cancer.
Enfortumab vedotin, also called EV (brand name Padcev), is an antibody-drug conjugate, or ADC. It pairs an antibody, a protein that finds a specific target on cancer cells, with a chemotherapy drug.
“The patient gets an antibody that targets the cancer cells specifically, and then the chemotherapy inside the cancer cell causes lesser side effects, better tolerability,” Dr. Bellmunt says.
What Did the VOLGA Trial Show?
Researchers enrolled people with MIBC who couldn’t get cisplatin or had turned it down, and who were planning to have surgery. Patients were randomly split into three groups:
- Durvalumab plus enfortumab vedotin (233 people): This group got three rounds of both drugs before surgery, then nine rounds of durvalumab alone after surgery.
- Durvalumab plus tremelimumab plus enfortumab vedotin (233 people): This group got the same plan mentioned above, plus a third drug, tremelimumab (brand name Imjudo), which releases a different brake.
- Surgery (229 people): This group had surgery followed by observation, or another approved treatment after surgery if one was available where they lived.
The main goal was to evaluate event-free survival, or how long people went without their cancer growing, coming back, or causing other major setbacks, or without dying from any cause.
The trial showed:
- At two years, 64% of people in the durvalumab plus EV group were event-free, compared with 45% in the surgery group. The gap showed up early. At one year, it was 73% versus 50%.
- The combination also helped people live longer (overall survival). At two years, 78% of people in the durvalumab plus EV group were alive, compared with 69% in the surgery group.
- In 45% of people in the durvalumab plus EV group, doctors found no cancer at all in the bladder tissue removed during surgery. This is called a pathologic complete response. In the surgery group, it was 10%.
“When the pathology was assessed, there is no tumor — meaning that this combination wipes completely out the presence of tumor in the bladder,” Dr. Bellmunt says of those patients.
That didn’t happen for everyone. More than half of the people who got the combination still had some cancer left at surgery. Doctors see a complete response as a hopeful sign for how someone may do over time.
The three-drug group also stayed event-free longer than the surgery group. But it hasn’t yet shown that people live longer. Researchers are still following these patients.
These are early results from a planned check-in on the data, after about two years of follow-up. Longer follow-up will tell us more.
Durvalumab + Enfortumab Vedotin Side Effects
Every cancer treatment has side effects.
In the durvalumab plus EV group, 30% of people had a serious side effect related to treatment. Serious means it may need medical care, a hospital stay, or a pause in treatment. In the three-drug group, it was 42%.
Side effects matched what doctors already know from each drug on its own. For EV, these include skin reactions and high blood sugar. They also include peripheral neuropathy, which is nerve damage that can cause numbness or tingling in the hands and feet. Each of these was serious in 5% of people or fewer.
In VOLGA, EV was given only before surgery. Other EV studies kept giving it afterward.
“We are only giving three cycles before the surgery. We are not giving it [EV] after the surgery… likely with the shorter treatment, it is going to be better,” Dr. Bellmunt says.
The trials have not compared the two approaches directly.
The Future: Can I Get the Treatment Now?
In the future, it is possible that some patients may not need bladder removal surgery, but that is not what the trial evaluated and not a question that can be answered right now.
“If we see a complete pathological response, maybe there is no need to remove the bladder in all patients,” Dr. Bellmunt explains.
As for the durvalumab and enfortumab vedotin treatment combination, the U.S. Food and Drug Administration (FDA) has given it priority review status, which means it will be evaluated by the administration faster and a decision is expected by the end of 2026.
Another combination, EV plus the immunotherapy drug pembrolizumab (brand name Keytruda), is already FDA-approved for treatment before and after surgery for MIBC. Ask your doctor whether it, or a clinical trial, could be right for you.
Dr. Bellmunt is hopeful about where the field is heading. NIAGARA was an earlier trial that added durvalumab to cisplatin-based chemo for patients who can take cisplatin.
“Based on the data of these trials [NIAGARA and VOLGA] we expect more patients are going to be cured, that’s the most important,” he says.
Questions to Ask Your Doctor
- Should I get treatment before and/or after bladder removal surgery?
- Why might durvalumab and enfortumab vedotin be a better option that cisplatin in my case?
- Am I eligible for this treatment combination?
- How will I be monitored while getting neoadjuvant/adjuvant therapy?
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