Can Padcev Plus Keytruda Help More Patients Beat Bladder Cancer?

For patients with muscle-invasive bladder cancer (MIBC), surgery to remove the bladder has long been a cornerstone of treatment. However, even after successful surgery, microscopic cancer cells can sometimes remain in the body and later grow into metastatic disease. This has led researchers to study whether additional treatments given before and after surgery can help eliminate the risk of recurrence.

At the 2026 ASCO Genitourinary Cancers (ASCO GU) Symposium, new findings from the KEYNOTE-B15 trial highlighted how combining the antibody-drug conjugate Padcev (enfortumab vedotin) with the immunotherapy Keytruda (pembrolizumab) may improve survival when used alongside surgery compared with traditional chemotherapy.

In an interview with CURE, Dr. Matthew Galsky discussed the background of the study, the key results presented at the meeting and what these findings could mean for patients considering treatment options. He is a professor of medicine (hematology and medical oncology), deputy director of the Mount Sinai Tisch Cancer Center (a NCI-designated Comprehensive Cancer Center), director of Genitourinary Medical Oncology, and co-director of the Center of Excellence for Bladder Cancer at the Mount Sinai Tisch Cancer Center.

You can read the full findings from the KEYNOTE-B15 study here!

CURE: Let's start with what you know about the KEYNOTE-B15 study. What were the background and the methodologies of the study?

Galsky: The KEYNOTE-B15 study was a study testing a new regimen of medications given intravenously before and after surgery to remove the bladder. The reason that we give medications intravenously before and after surgery when patients have MIBC is because, with surgery alone, a subset of patients will have the cancer show up somewhere else months to years later. That is called metastatic disease.

When metastatic disease happens, it is because even before the bladder was removed, microscopic cancer cells disseminated from the original tumor to elsewhere in the body. These are too small to be seen, but over time, those cells can grow. We give this medication intravenously to try and eradicate those cells and to help the surgery that is taking care of the primary tumor.

Cisplatin-based chemotherapy given for about three months before surgery has been the standard of care for about 25 years, and it has been hard to beat that. There were a few attempts, but it remained the standard. Now, for patients with bladder cancer that has spread, we use a new regimen as of a few years ago that was shown to be much better than our older chemotherapy.

This new regimen is comprised of two drugs. One of them is called an antibody-drug conjugate, which is a protein designed to bind to cancer cells with chemotherapy attached to it. Some people have described it as a sort of "smart bomb" approach, as it tries to deliver chemotherapy more specifically to the intended target. It is given with a drug called Keytruda, which is an immune checkpoint inhibitor (loosely called immunotherapy) that tries to get the body’s immune system to fight cancer.

Since that combination has become our standard treatment for metastatic bladder cancer, it was logical to move this regimen earlier to the muscle-invasive setting to see if we could cure more patients by giving it with surgery compared to our older chemotherapy.

Could you please explain the key takeaways from the KEYNOTE-B15 study that were presented at ASCO GU? What should patients know about the results of this research?

The study randomized 808 patients to this new regimen with surgery versus our older regimen with surgery. The primary end point of the study is something we call event-free survival, which is basically the amount of time before cancer comes back or worsens.

There was a substantial reduction in the likelihood of cancer progressing or coming back with the new regimen compared to the older one. There was also a significantly longer time that patients lived with the newer regimen, suggesting that, yes, we are curing more patients with MIBC with this new approach.

Something that many patients worry about is whether adding more treatment before and after surgery will delay surgery or maybe even make recovery harder. What did this study show about safety and the ability of patients to still get surgery?

Anytime we introduce new systemic therapies or medications before surgery to remove the bladder, we want to be mindful that we are not compromising the ability to have surgery or impacting the recovery process. Those parameters are always carefully monitored.

In studies like this, there was no difference in the ability to proceed with surgery on either arm of the study — the control arm versus the new treatment — and there was no clear increase in perioperative complications with the new regimen compared to the older regimen.

If these results do change the standard of care, what questions should patients ask their care team now about neoadjuvant and adjuvant treatment options for their MIBC?

Right now, this regimen is approved for use in patients with MIBC based on a sister study. That study used the same regimen with a slight nuance in terms of how many cycles were administered, but compared the regimen plus surgery versus surgery alone for patients who could not receive cisplatin-based chemotherapy. That represents about 50% of our patient population, most commonly because impairment in kidney function makes it so we cannot give cisplatin safely.

That sister study also showed a marked benefit, leading to FDA approval in that specific setting.

Based on the results of this current study, which show very consistent results, there is the anticipation that this could become a standard regimen for all patients with MIBC. If that is the case, an individual with MIBC should really be asking their physicians: "Is this regimen right for me? Is there any contraindication to me getting these drugs? And do you think this regimen will increase the likelihood that the cancer won't come back in the future if I proceed with this approach?"

Transcript has been edited for clarity and conciseness.

References

1. “Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study,” by Dr. Matthew Galsky, et al. Journal of Clinical Oncology.

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