Eighty percent of those on pembrolizumab (illustrated above) with trimodal therapy had no detectable signs of their cancer spreading after two years.
Credit: Getty / BEHNOUSH HAJIAN / SCIENCE PHOTO LIBRARY
A drug that helps the immune system find cancer cells also helps patients avoid having their bladders surgically removed (cystectomy), a new study shows. The findings apply to serious cases after tumors have already spread into the bladder’s surrounding muscle wall.
Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the phase 2 study showed that adding pembrolizumab, also known as Keytruda, to standard chemotherapy and radiation with surgery (trimodal therapy) allowed 60 percent of patients to avoid bladder removal for up to two years after treatment, when the study concluded.
About a third of patients diagnosed with bladder cancer have the muscle-invasive form and face the prospect of losing their bladder, which can lead to serious declines in quality of life. Patients who lose their bladder must find another means of getting rid of their urine, the researchers said.
Alternatives include reconstructing a new bladder from intestinal tissue or using an external pouch to collect urine. These methods come with added risk of infection, discomfort, pain, and kidney stones.
, the study is believed to be the largest of its kind, involving 54 men and women being treated at five medical centers in the United States for muscle-invasive urothelial cancer of the bladder.
“Our study provides the largest evidence to date that pembrolizumab, when combined with standard chemotherapy and radiation, can safely and effectively be used in combination with surgery to preserve the bladder in those with bladder cancer that has spread to the surrounding muscles,” said study lead investigator Minas P. Economides, MD.
The use of immunotherapy in combination with standard treatments has transformed care and improved survival for many patients with lung, breast, and ovarian cancers, as well as more severe cases of bladder cancer.
Among the phase 2 study’s other key results was that 80 percent of patients on pembrolizumab with trimodal therapy showed no sign of cancer spread (metastasis) after two years. Patients’ overall survival rate after two years was 81 percent. Adverse events, the researchers said, were mostly related to toxicity from chemotherapy and radiation and were considered manageable by restricting doses.
“Patients can have hope that more treatment options are being studied to improve their survival outcomes and quality of life, even after a diagnosis of muscle-invasive bladder cancer,” said Dr. Economides, an assistant professor of medicine at NYU Grossman School of Medicine and an oncologist at Perlmutter Cancer Center.
“Our findings warrant further phase 3 clinical trials that, if successful, could make the addition of immune-based therapies, such as pembrolizumab, the new standard of care for muscle-invasive bladder cancer when used in combination with chemoradiation and surgery,” said study co-investigator David R. Wise, MD, PhD, an associate professor in the Departments of Medicine and at NYU Grossman School of Medicine and an oncologist at Perlmutter Cancer Center. “This is so patients can best maintain their quality of life by preserving and keeping their own bladder.”
Dr. Wise notes that a phase 3 trial would directly compare treatment options in a larger number of similar patients, with some using combination immunotherapy and others not.
Researchers believe that combining immunotherapy with traditional trimodal therapy is a natural fit. The chemotherapy drug gemcitabine enhances the ability of immune cells to destroy cancer cells while pembrolizumab prevents the cancer cells from hiding from these immune cells.
Funding for this phase 2 study was provided by Merck & Co., the manufacturer of pembrolizumab. Additional study support came from National Institutes of Health grant P30CA016087.
In addition to Drs. Economides and Wise, NYU Langone researchers involved in this study were co-investigators Jesse Persily, MD; Tsivia Hochman, MS; ; Kaitlyn Francese, MSN; Sarah Griglun, MPH; Dayna A. Leis, NP; James S. Wysock, MD; Peter B. Schiff, MD, PhD; Nicholas Sanfilippo, MD; Samir Taneja, MD; and William C. Huang, MD.
Dr. Economides receives honoraria from Merck and Aveo. Dr. Wysock is a consultant for Focal One and Uro 1. Dr. Huang is an investigator for Merck and Pfizer, and is also an investigator for Urogen-sponsored projects. Dr. Wise is a paid consultant for Pfizer, Bayer, K36, Oncoc4, AstraZeneca, Janssen, and BioNTech. The terms and conditions of all these relationships are being managed in accordance with the policies of NYU Langone Health.
Other researchers were study co-investigators Peter O’Donnell, MD, and Randy Sweis, MD, at the University of Chicago; Ajjai Alva, MS, and Phillip Palmbos, MD, PhD, at the University of Michigan; Matthew Milowsky, MD, and Tracy Rose, MD, MPH, at the University of North Carolina at Chapel Hill; Marisa Kollmeier, MD, Scot Niglio, MD, and Gopakumar Iyer, MD, at Memorial Sloan Kettering Cancer Center; Daniel Spratt, MD, at Case Western Reserve University; and study senior investigator Arjun Balar, MD, at Volastra Therapeutics.
About NYU Langone Health
NYU Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked NYU Langone No. 1 out of 118 comprehensive academic medical centers across the nation for four years in a row, and U.S. News & World Report recently ranked four of its clinical specialties No. 1 in the nation. NYU Langone offers a comprehensive range of medical services with one high standard of care across seven inpatient locations, its Perlmutter Cancer Center, and more than 320 outpatient locations in the New York area and Florida. The system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise.
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