Pembrolizumab in combination with gemcitabine and concurrent hypofractionated radiation therapy and maximal transurethral resection may be safe and feasible in patients with muscle-invasive bladder cancer (MIBC), allowing many patients to potentially avoid cystectomy, according to the results of a multicenter phase II trial published in European Urology.
“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, Assistant Professor of Medicine at NYU Grossman School of Medicine and Oncologist at Perlmutter Cancer Center.
Study Methods
Patients with MIBC (n = 54) were enrolled in the multicenter phase II trial and received one dose of pembrolizumab followed by maximal transurethral resection and then definitive bladder radiation therapy plus concurrent low-dose gemcitabine and pembrolizumab given every 3 weeks for three doses.
The primary endpoint of the study was the 2-year bladder-intact disease-free survival rate, with secondary endpoints including safety, metastasis-free survival, and overall survival.
Key Findings
A total of 48 patients were included in the efficacy analysis. At 2 years, the bladder-intact disease-free survival rate was 60% (95% confidence interval [CI] = 45%–73%), the metastasis-free survival rate was 81% (95% CI = 66%–92%), and the overall survival rate was 83% (95% CI = 69%–91%).
Treatment-related adverse events of grade 3 or higher were observed in one-quarter of patients.
“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 [MIBC],” said Dr. Economides.
“Our findings warrant further phase III clinical trials that, if successful, could make the addition of immune-based therapies, such as pembrolizumab, the new standard of care for [MIBC] cancer when used in combination with chemoradiation and surgery,” said study co- investigator David R. Wise, MD, PhD, Associate Professor in Medicine and Urology at NYU Grossman School of Medicine and Oncologist at Perlmutter Cancer Center. “This is so patients can best maintain their quality of life by preserving and keeping their own bladder.”
DISCLOSURES: Funding for this phase 2 study was provided by Merck & Co., the manufacturer of pembrolizumab. Additional study support came from a National Institutes of Health grant. 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 a consultant, speaker, and investigator for Urogen. 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. For full disclosures of the other study authors, visit sciencedirect.com.
