illustration of a bladder surrounded by cancer cells

Bladder Cancer Breakthrough Dramatically Extends Survival 


People with advanced urothelial cancers — most of whom have bladder cancer — now have a new first-line treatment that will extend their survival for the first time in almost 40 years. The new treatment, approved by the Food and Drug Administration (FDA) on December 15, combines pembrolizumab, an immunotherapy agent, with enfortumab vedotin, an antibody drug conjugate.

The FDA had previously approved the drug combination in April for people who are ineligible for cisplatin-containing chemotherapy, a much smaller group of people. Bladder cancer is the fifth most common cancer.

Data from a phase three clinical trial, presented at the European Society of Medical Oncologists in October, showed that the experimental therapy nearly doubled the median survival to 31.5 months, compared to an average survival of just 16.5 months in the standard chemotherapy arm. Progression-free survival also doubled.

Furthermore, a slowing of the progression rate after 18 months in almost 40% of the experimental arm suggests that some people may live much longer. Historically, only 5% of advanced bladder cancer patients survived five years.

Some People Already Receiving the New Drug Combination

Because the FDA previously approved this new treatment for use later in the course of metastatic bladder cancer, oncologists at the Duke Cancer Institute said that they have already been using the combination.

Christopher Hoimes, DO, a medical oncologist in the DCI Center for Prostate and Urologic Cancers, said that people with urothelial cancer should visit a comprehensive cancer center to see if the treatment is right for them and to develop a guidance plan on dosing and management.

A Role in the Drug’s Early Development

Hoimes has been studying this breakthrough treatment combination since 2017, when he was part of a team developing the idea for the combination.

Hoimes' reasons for believing that the two agents would work well together were complex, but he boiled down his thinking to this: targeting the cancer’s surface adhesion receptors could potentially enhance the immune response.

Despite having a sound scientific rationale for how the combination would work, he understood that the odds were against him in a field where hundreds of cancer therapies and combinations had been tested and failed for this intractable disease.

Convincing Two Companies to Work Together

Another matter threatening to hinder progress was that the drugs Hoimes wanted to study were owned by two different companies — pembrolizumab by Merck, and enfortumab vedotin by Seattle Genetics (now Seagen Inc.).

Companies are typically reluctant to combine an investigational product to other treatments because they can limit their indications and increase side effects, according to medical oncologist Daniel George, MD, director of the DCI Center for Prostate and Urologic Cancers, who was not involved in the trial. To do so, they must be convinced that a collaboration is worth the risk, extra time, and resources, said George.

What motivated Hoimes to push for the two companies to study the combination, he said, was his passion for studying bladder cancer and generating similar enthusiasm amongst the pharmaceutical teams to work together to improve outcomes for patients.

Hoimes felt frustrated after years of watching patients suffer through months of grueling chemotherapy and life-altering surgery that rewarded them with only a small increase in survival. And too many of his patients weren’t even eligible to get the chemotherapy, he said.

Hoimes and the team of investigators convinced the two companies to work together on a phase one study, for which he served as principal investigator (PI). Positive data from that trial led to a phase two study, which Hoimes also led, and an FDA accelerated approval for the combination for a select population in April of 2023.

Outlook for Advanced Bladder Cancer May Improve Even More

The outlook for people with aggressive bladder cancer may improve even more in the future, after completion of an ongoing phase three study of this same drug combination in the perioperative setting — before and after people undergo surgery — to try and stop the cancer from spreading.

Hoimes is a lead PI and on the scientific committee for the international study, called Keynote-B15, which has recently fully enrolled.

“This trial raises the stakes even more. This is the curative-intent setting, where a greater proportion of patients with urothelial cancer who are candidates for surgery . . .  may be cured of their disease. I’m certainly hopeful for similarly stunning results as what we just had for patients who are metastatic, but we need to wait for the data to guide us in this earlier-stage surgical setting,” he said.

This page was reviewed on 12/19/2023