Durvalumab plus enfortumab vedotin before surgery improves survival in bladder cancer

A phase 3 trial has found that adding durvalumab and enfortumab vedotin around bladder removal surgery improves outcomes for people with muscle-invasive bladder cancer who cannot, or will not, take cisplatin chemotherapy. Compared with surgery alone, the two-drug regimen was associated with a 42% lower risk of death and a 49% lower risk of recurrence, progression or other cancer-related events. The results from the VOLGA trial, co-led by researchers at the UCLA Health Jonsson Comprehensive Cancer Center, were published in the New England Journal of Medicine.

A gap in standard care

Muscle-invasive bladder cancer has grown into the muscular wall of the organ. Treatment usually means removing the bladder, ideally preceded by cisplatin-based chemotherapy to lower the chance of relapse. According to senior author Dr Alexandra Drakaki, nearly half of patients cannot have this chemotherapy, because of kidney impairment, hearing loss, nerve damage or other conditions. These patients have often gone straight to surgery with no drug treatment beforehand.

Trial design

VOLGA enrolled 695 patients at 229 centres in 25 countries. All were ineligible for cisplatin or had declined it. Participants were randomly assigned to one of three arms:

• durvalumab plus enfortumab vedotin before surgery, then durvalumab alone afterwards;
• the same regimen with a second immunotherapy drug, tremelimumab, added;
• surgery alone.

Enfortumab vedotin is an antibody-drug conjugate that binds nectin-4, a protein found on many bladder tumour cells, and delivers a cytotoxic payload. Durvalumab blocks PD-L1, a protein tumours can exploit to avoid immune attack. Enfortumab vedotin was given only before surgery, whereas some other recent regimens continue it afterwards.

What the results show

At two years, 78.4% of patients on the two-drug regimen were alive, against 69.4% in the surgery-alone group. Freedom from recurrence, progression or other cancer-related events was 63.5% versus 45.1%.

The gap was also large in the surgical specimens. No detectable cancer remained in 45.1% of patients who had the two-drug treatment, compared with 9.6% of those who had surgery alone.

The three-drug arm also significantly reduced the risk of cancer-related events or death relative to surgery alone. However, it had not shown a statistically significant gain in overall survival at this stage of follow-up.

Safety and caveats

Severe side effects were more common in the treatment arms than with surgery alone. The investigators reported no unexpected safety signals for the two-drug combination, and it did not appear to raise surgical complications. Because the comparator was surgery alone, the trial does not show how the regimen compares with other perioperative strategies. The survival figures are two-year estimates, so longer follow-up will be needed to judge durability.

Why it matters

For clinicians and trialists, the study provides randomised evidence for a neoadjuvant option in a group with few alternatives. The design also raises a practical question: whether the targeted drug can be limited to the pre-operative phase, with immunotherapy alone afterwards, without losing benefit. Drakaki suggested this could ease treatment and financial burden during recovery from a major operation, though the trial was not set up to test that directly.

Further follow-up is planned to clarify whether the three-drug combination improves overall survival. Researchers will also be watching for longer-term safety data and for work identifying which patients gain most from the regimen. The trial report is by Thomas Powles and colleagues.

Source: New drug combination improves survival in patients with muscle-invasive bladder cancer (Medical Xpress, 10 November 2026).

Image: AI-generated illustration.