ASCO GU 2019: Pembrolizumab in Muscle-Invasive and Locally Advanced Urothelial Carcinoma - AMBASSADOR versus Observation

San Francisco, CA ( Patients with high-risk muscle-invasive bladder cancer (MIBC) have a poor prognosis. Adjuvant cisplatin-based neoadjuvant chemotherapy has been shown to improve survival, but a large number of these patients are resistant to chemotherapy and develop recurrent disease. Due to renal insufficiency, many patients are also not cisplatin-eligible.  Therefore, there is a need to develop additional treatment options. As part of the Trials in Progress Poster Session B at the 2019 Genitourinary Urinary Cancers Symposium, Dr. Andrea Apolo, a medical oncologist from the National Institutes of Health presented the trial design for the AMBASSADOR trial, a Phase III randomized clinical trial evaluating the efficacy of pembrolizumab in patients with muscle-invasive and locally advanced urothelial carcinoma versus observation alone. 

Eligible patients for the trial have high-risk muscle-invasive bladder cancer or upper tract urothelial carcinoma (UTUC).  They must have undergone a cystectomy or nephrectomy within 16 weeks.  Finally, they must have pT2-4aNx or pTxN+ disease after having undergone neoadjuvant chemotherapy.  Alternatively, patients can have pT3-4Nx or pN+ disease post surgery with no chemotherapy.  Patients will then be stratified by PDL-1 positivity, receipt of prior neoadjuvant chemotherapy, and pathologic stage pT2/3/4aN0 vs. pT4bNx or N1-3 disease.  They will then be randomized to receive 200mg of pembrolizumab every three weeks for 12 months or to observation alone. Patients will then be monitored for disease recurrence and medication tolerability.  Healthcare-related quality of life outcomes will also be measured.

The primary objectives of this study are to determine the disease-free survival (DFS) and overall survival (OS) in patients with muscle-invasive bladder or upper-tract urothelial carcinoma who are treated with adjuvant pembrolizumab versus observation.  Secondary endpoints include determination of safety and tolerability of pembrolizumab in patients with this disease state.

The study is clinically significant, as it will help determine if adjuvant pembrolizumab for patients with high-risk MIBC or UTUC can help reduce the risk of disease progression, RFS, and OS. 

Presented by: Andrea B. Apolo, MD, National Institutes of Health, Bethesda, Maryland

Written by: Brian Kadow, MD. Society of Urologic Oncology Fellow, Fox Chase Cancer Center at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA