Durvalumab + BCG continues to deliver in high-risk NMIBC
Longest-running NMIBC trial shows sustained disease-free survival benefit and delayed cystectomy at five years.
Updated results from the POTOMAC trial show continued improvement in disease-free survival, overall survival and time to cystectomy with durvalumab plus bacillus Calmette-Guérin (BCG) in patients with high-risk, non-muscle invasive bladder cancer (NMIBC). With five years of follow-up and counting, POTOMAC is already the longest-running clinical trial in NMIBC.
“These data clearly support one year of durvalumab with induction maintenance of BCG as a potential new treatment with high-risk NIMBC,” said Neal Shore, MD, medical director of the START Carolinas/Carolina Urologic Research Center in Myrtle Beach, South Carolina. “The safety of durvalumab plus BCG in the overall safety population and across papillary subgroups was consistent with the known safety profiles of BCG and durvalumab.”
Dr. Shore updated the efficacy and safety findings of POTOMAC in the first Practice-Changing, Paradigm-Shifting Clinical Trials presentation during Friday’s Plenary Session. Initial data were presented in 2025 and published in The Lancet.
Early high-risk disease recurrence is associated with worse outcomes in NMIBC, and BCG unresponsiveness is an accepted indication for radical cystectomy. The initial results showed that adding one year of durvalumab to BCG was associated with a significant improvement in disease-free survival (DFS), with a hazard ratio (HR) of 0.68 and a nonsignificant trend toward improved overall survival (OS).
Five-year data presented on Friday showed the same 32% improvement in DFS, along with an overall decline in the number of early high-risk events and a delay in time to the first high-risk event. There was also a clinically significant delay in time to cystectomy: 14 months with BCG only versus 19 months with durvalumab + BCG, HR 0.63. The addition of durvalumab did not affect a patient’s ability to receive adequate BCG therapy
Dr. Shore noted that while median cystectomy-free survival has not yet been reached, the durvalumab cohort already shows a statistically significant improvement, HR 0.69.
Most patients in the trial had papillary tumors, and there was a reduction in high-risk disease recurrence or death across papillary subtypes, HR 0.56. The median OS has not yet been reached, but the survival trend continues to favor durvalumab, HR 0.80.
Adverse events (AEs) were common, with 88% of patients showing some sort of AE that could be related to treatment. About a quarter of AEs (23%) were grade 3-4, and 13% were serious. Similar numbers of AEs leading to discontinuation were likely due to durvalumab (16%) and BCG (15%). Some 27% of AEs were immune-mediated events.
“Immune-mediated adverse events are important for our colleagues to become comfortable with,” Dr. Shore said. “The most common things are thyroid events, followed by hepatic events and rash. The majority of these resolve with interruption, topical treatment and the potential use of steroids.”
