ASCO GU 2019: A Phase III, Randomized, Open-label, Multicenter, Global Study of Durvalumab and BCG versus BCG Alone in High-risk, BCG-naïve Non-muscle-invasive Bladder Cancer Patients - POTOMAC

San Francisco, CA ( While the standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) is currently maximal transurethral resection of the bladder tumor (TURBT), followed by an induction course of BCG, recurrence rates can reach as high as 50% in this patient population. Because recurrence rates are high after induction BCG alone, the Dr. Maria De Santis from Charite University Hospital in Berlin, Germany, and her group sought to evaluate if combination anti-PD1 or anti-PDL-1 agents with BCG would lead to decreased recurrence rates and improved cancer-specific outcomes. As part of the Trials in Progress Poster Session B at the 2019 Genitourinary Cancers Symposium in San Francisco, she presented the trial design of the POTOMAC trial, a phase III randomized, open-label, multicenter study comparing Durvalumab in combination with intravesical BCG versus intravesical BCG alone in patients with high-risk, BCG-naïve, non-muscle invasive bladder cancer (MIBC).    

They are enrolling approximately 1300 patients with histologically proven high-risk NMIBC which has been completely resected.  Candidates for enrollment must be BCG-naïve. Patients are being randomized in a 1:1:1 fashion to receive induction and maintenance BCG alone, induction BCG with 13 cycles of Durvalumab, and induction and maintenance BCG with 13 cycles of Durvalumab. The primary outcome of the study is the assess disease-free survival (DFS). Secondary endpoints include the proportion of patients alive and disease free at 24 months and overall survival. They will additionally assess for the safety and tolerability of Durvalumab in this patient population.  Finally, they will look at the health-related quality of life outcomes.  Patients must have never received prior immunotherapy or intravesical therapy.  Other exclusion criteria include muscle-invasive, extravesical disease, or any metastatic disease. They hope to follow patients for up to 5 years after the last enrollment to have adequate time to assess for outcomes. 

Dr. De Santis concludes that there is an important need for more effective therapies in patients with high-risk NMIBC in order to reduce recurrence rates.  Prior data on PD-1 and PDL-1 inhibitors in other stages of bladder cancer have suggested their efficacy in slowing progression and overall survival.  She believes that this trial may help to suggest how we can more effectively treat patients with high-risk NMIBC with combination BCG and immunotherapy. She hopes to present this data in the near future once the trial has accrued and the data has matured.  

Presented by: Maria De Santis, MD, Charite University Hospital in Berlin, Germany

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