In a trial of 808 people, 79.4 percent of those given two newer drugs before and after bladder surgery were alive with no return of their cancer two years later, against 66.2 percent on the standard chemotherapy.
Two in three. That is how many people with muscle-invasive bladder cancer, a tumour that has grown into the muscle wall of the bladder, were still alive and free of their disease two years after the chemotherapy that has been a standard treatment for it. In a trial of 808 patients, replacing that chemotherapy with two newer drugs, given before surgery and continued after it, lifted the figure to four in five. The US Food and Drug Administration approved the new combination for these patients on 10 July 2026, and the full results were published in the New England Journal of Medicine on 22 July.
How we know
The trial, KEYNOTE-B15/EV-304, randomly assigned 808 adults whose bladder cancer had reached the muscle wall and who were fit enough for both cisplatin chemotherapy and surgery to remove the bladder. Of them, 405 were given four cycles of enfortumab vedotin and pembrolizumab before that surgery, then further doses after it. Enfortumab vedotin carries a cell-killing agent to tumour cells that display a surface marker called nectin-4, which is overexpressed in bladder cancer among others; pembrolizumab is an immunotherapy, a treatment that works by changing how the patient's own immune cells behave, and it blocks a receptor that would otherwise hold those cells back from attacking a tumour. The other 403 patients received the standard four cycles of cisplatin and gemcitabine, then surgery.
After a median 33.6 months of follow-up, 79.4 percent of the first group were alive at two years with no return or progression of their cancer, against 66.2 percent of the second. That measure, event-free survival, was what the trial set out to test, and it was assessed by an independent panel kept unaware of which treatment each patient had received. Two-year overall survival was 86.9 percent against 81.3 percent. And 55.8 percent of the first group had no cancer left to find in the tissue taken at surgery, a pathological complete response, against 32.5 percent. KEYNOTE-B15/EV-304 was an open-label trial, meaning patients and their doctors knew throughout which treatment they were receiving, and the companies that make the drugs funded it.
Why it matters
For patients well enough for it, treating muscle-invasive bladder cancer means removing the bladder, the operation both groups in this trial were heading for. Everything given beforehand is an attempt to make it count: to shrink the tumour, and to stop the disease returning once the bladder is gone. Cisplatin chemotherapy has been a standard part of that attempt. This trial set a different approach against it directly, pairing an immunotherapy with a drug that delivers its payload to marked tumour cells, and the newer pair came out ahead on all three outcomes compared: event-free survival at two years was 13.2 percentage points higher, overall survival 5.6 points higher, and the share of patients with no cancer left to find at surgery 23.3 points higher. Those gains came with more severe side effects, and so far with an approval that stops at the United States border. Six regulators read the same application together. Five are still reading.
The new regimen is harder to tolerate: side effects graded 3 or higher, the levels doctors class as severe, affected 75.7 percent of the group given enfortumab vedotin and pembrolizumab, against 67.2 percent on chemotherapy. The trial was run without blinding, so patients and their doctors knew which treatment each person was receiving, and the drug makers funded it. Median survival has not been reached in either group, so how far the survival gap widens or narrows over time is not yet known. And the combination is approved so far only in the United States, with reviews still running at the Australian, Canadian, Swiss, British and Israeli regulators.
What are the two drugs?
Enfortumab vedotin, sold as Padcev, is built from an antibody that binds a surface marker called nectin-4, common on bladder tumour cells, and carries a cell-killing agent to them. Pembrolizumab, sold as Keytruda, blocks a receptor called PD-1 on immune cells and so releases them to attack a tumour. In the trial the two were given together, four cycles before surgery and further doses after it.
Do patients live longer?
Two years after treatment, 86.9 percent of the group given the new pair were alive, against 81.3 percent of those on chemotherapy. Median survival has not yet been reached in either group, so how large that gap becomes over time is not known. The trial's main measure was the share alive with no return or progression of the cancer, which was 79.4 percent against 66.2 percent at two years.
Is it harder to tolerate?
Yes. Side effects graded 3 or higher affected 75.7 percent of patients on the new regimen, against 67.2 percent on chemotherapy. The prescribing information carries warnings for skin reactions, high blood sugar, lung inflammation, nerve damage and eye disorders with enfortumab vedotin, and for immune-mediated reactions with pembrolizumab.
Can patients outside the United States get it?
Not yet. The FDA approved the regimen on 10 July 2026 under Project Orbis, a scheme for reviewing cancer drugs in several countries at once, alongside regulators in Australia, Canada, Switzerland, the United Kingdom and Israel. Those five reviews were still under way when the US approval was announced.
- New England Journal of Medicine, Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer (KEYNOTE-B15/EV-304) Primary
- US Food and Drug Administration, FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer
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