Bladder Cancer Breakthrough Dramatically Extends Survival
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From the Duke Cancer Institute archives. Content may be out of date.
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.
New research from Duke Cancer Institute (DCI) is helping uncover why some bladder cancer patients are less likely to benefit from a common treatment and how a patient’s cancer history may help guide more personalized care decisions in the future.For more than 50 years, Bacillus Calmette-Guérin (BCG) treatment has been the standard of care for patients with early-stage bladder cancer. It helps reduce the chances that cancer will come back after surgery, and it works well for many patients. But not all bladder cancers behave the same.Bladder cancer is one form of a broader group known as urothelial cancers, which can develop anywhere along the urinary tract. Most cases begin in the bladder itself and are often caught early because patients develop symptoms, such as blood in the urine. These early-stage cancers are typically treated with surgery followed by BCG, which is delivered directly into the bladder to help prevent recurrence.However, about 10 percent of urothelial cancers originate in the upper urinary tract—in the kidneys or ureters. Even after those tumors are treated, cancer can later reappear in the bladder.“Historically, we’ve treated these bladder recurrences the same way we treat primary bladder cancer,” said Yu Guang Tan, MD, a urology fellow at Duke and a collaborator from Duke-NUS Medical School in Singapore. “But the question is, are they really the same disease?”In a recent study published in Urologic Oncology, Tan worked with colleagues including Michael Abern, MD, co-chair of the DCI Center for Prostate and Urologic Cancers, to explore whether bladder cancers that arise after upper tract disease respond differently to BCG than cancers that originate in the bladder.Across both a single-institution study and a larger systematic review and meta-analysis of more than 1,300 patients worldwide, the team found a consistent pattern: patients with a history of upper tract urothelial cancer were significantly more likely to experience recurrence or disease progression after BCG treatment.“In some cases, nearly half of these patients did not respond well to BCG,” Tan said. “That’s a substantial number, and it suggests we may need to think differently about how we treat this group.”BCG has long been the backbone of therapy for non-muscle invasive bladder cancer, but it is not without limitations. In addition to variable effectiveness, the treatment has also faced periodic shortages, particularly in smaller or rural care settings.“This research gives us another piece of the puzzle,” Abern said. “If a patient has a history of upper tract disease, it may shape expectations about how well BCG will work and whether we should consider other options sooner, including clinical trials.”Tan and Abern both emphasize that BCG remains an important and effective therapy for many patients. The goal is not to replace it, but to better match treatments to the patients most likely to benefit.One of the most important implications of the study is its potential role in advancing precision medicine for bladder cancer. The team found that while these cancers may look similar under the microscope, they are likely biologically distinct. That difference may explain why they respond differently to treatment.“We think this history of upper tract cancer may act as a clinical biomarker,” Tan said. “It helps us predict how a patient might respond, but we still need to understand the biology behind it.”To answer that question, the researchers are now conducting whole genome sequencing studies to identify the genetic differences between these tumor types. They are also building a joint database between Duke and Duke-NUS to uncover additional factors that may influence treatment outcomes.“It’s an exciting time in bladder cancer research,” Tan said. “We have many new therapies emerging, and the challenge now is figuring out which treatment is best for which patient.”The research reflects a strong international partnership between Duke University and Duke-NUS Medical School in Singapore. By bringing together data from multiple countries and healthcare systems, the team was able to confirm that these findings are consistent across diverse patient populations.“That global perspective is really important,” Abern said. “It shows that this trend holds true across different regions, which makes the findings more robust and meaningful.”As new therapies, including immunotherapy and targeted treatments, continue to emerge, studies like this one will play a key role in shaping how patients are selected for different treatment approaches.“By better understanding these differences, we can improve how we counsel patients, design clinical trials, and ultimately deliver more personalized care,” Abern said.
New research from Duke Cancer Institute (DCI) is helping uncover why some bladder cancer patients are less likely to benefit from a common treatment and how a patient’s cancer history may help guide more personalized care decisions in the future.For more than 50 years, Bacillus Calmette-Guérin (BCG) treatment has been the standard of care for patients with early-stage bladder cancer. It helps reduce the chances that cancer will come back after surgery, and it works well for many patients. But not all bladder cancers behave the same.Bladder cancer is one form of a broader group known as urothelial cancers, which can develop anywhere along the urinary tract. Most cases begin in the bladder itself and are often caught early because patients develop symptoms, such as blood in the urine. These early-stage cancers are typically treated with surgery followed by BCG, which is delivered directly into the bladder to help prevent recurrence.However, about 10 percent of urothelial cancers originate in the upper urinary tract—in the kidneys or ureters. Even after those tumors are treated, cancer can later reappear in the bladder.“Historically, we’ve treated these bladder recurrences the same way we treat primary bladder cancer,” said Yu Guang Tan, MD, a urology fellow at Duke and a collaborator from Duke-NUS Medical School in Singapore. “But the question is, are they really the same disease?”In a recent study published in Urologic Oncology, Tan worked with colleagues including Michael Abern, MD, co-chair of the DCI Center for Prostate and Urologic Cancers, to explore whether bladder cancers that arise after upper tract disease respond differently to BCG than cancers that originate in the bladder.Across both a single-institution study and a larger systematic review and meta-analysis of more than 1,300 patients worldwide, the team found a consistent pattern: patients with a history of upper tract urothelial cancer were significantly more likely to experience recurrence or disease progression after BCG treatment.“In some cases, nearly half of these patients did not respond well to BCG,” Tan said. “That’s a substantial number, and it suggests we may need to think differently about how we treat this group.”BCG has long been the backbone of therapy for non-muscle invasive bladder cancer, but it is not without limitations. In addition to variable effectiveness, the treatment has also faced periodic shortages, particularly in smaller or rural care settings.“This research gives us another piece of the puzzle,” Abern said. “If a patient has a history of upper tract disease, it may shape expectations about how well BCG will work and whether we should consider other options sooner, including clinical trials.”Tan and Abern both emphasize that BCG remains an important and effective therapy for many patients. The goal is not to replace it, but to better match treatments to the patients most likely to benefit.One of the most important implications of the study is its potential role in advancing precision medicine for bladder cancer. The team found that while these cancers may look similar under the microscope, they are likely biologically distinct. That difference may explain why they respond differently to treatment.“We think this history of upper tract cancer may act as a clinical biomarker,” Tan said. “It helps us predict how a patient might respond, but we still need to understand the biology behind it.”To answer that question, the researchers are now conducting whole genome sequencing studies to identify the genetic differences between these tumor types. They are also building a joint database between Duke and Duke-NUS to uncover additional factors that may influence treatment outcomes.“It’s an exciting time in bladder cancer research,” Tan said. “We have many new therapies emerging, and the challenge now is figuring out which treatment is best for which patient.”The research reflects a strong international partnership between Duke University and Duke-NUS Medical School in Singapore. By bringing together data from multiple countries and healthcare systems, the team was able to confirm that these findings are consistent across diverse patient populations.“That global perspective is really important,” Abern said. “It shows that this trend holds true across different regions, which makes the findings more robust and meaningful.”As new therapies, including immunotherapy and targeted treatments, continue to emerge, studies like this one will play a key role in shaping how patients are selected for different treatment approaches.“By better understanding these differences, we can improve how we counsel patients, design clinical trials, and ultimately deliver more personalized care,” Abern said.
