Durvalumab Plus BCG Improves DFS in High-Risk Non–Muscle-Invasive Bladder Cancer

NMIBC | Image credit:

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The addition of durvalumab (Imfinzi) to standard-of-care BCG induction and maintenance therapy led to a statistically significant and clinically meaningful improvement in disease-free survival (DFS) vs BCG induction and maintenance alone in patients with high-risk non–muscle-invasive bladder cancer (NMIBC), according to topline findings from the phase 3 POTOMAC trial (NCT03528694).1

A descriptive analysis also indicated no detriment in overall survival (OS) although the trial was not statistically powered to formally evaluate OS.

The safety profile of the induction and maintenance regimen was comparable to that of the individual agents, and no new safety signals were identified. Moreover, the likelihood of patients completing BCG induction and maintenance was not affected by the addition of durvalumab.

The second investigational arm comparing durvalumab plus BCG as induction only vs BCG induction and maintenance therapy alone did not meet the end point for DFS. These data will be presented at an upcoming medical meeting and shared with global regulatory agencies.

“These exciting data show that adding one year of durvalumab to the current standard treatment significantly extends the time patients live without high-risk disease recurrence or progression. While most patients with NMIBC are treated with curative intent, 80% see their disease return and almost half may require life-altering surgery to remove the bladder, underscoring the urgent need to improve treatment,” Maria De Santis, MD, head of the Interdisciplinary Uro-Oncology Section at Charité Universitätsmedizin Berlin in Germany, and a principal investigator of the POTOMAC trial, said in a news release.

POTOMAC is an open-label, multicenter, global trial evaluating durvalumab plus BCG induction and maintenance therapy (n = 325) and durvalumab plus BCG induction only (n = 325) vs BCG induction and maintenance alone (n = 325) in patients with high-risk NMIBC.2

To be eligible for enrollment patients need to have a high-risk tumor defined as a T1 tumor, high-grade or grade 3 disease, carcinoma in situ, or multiple and recurrent and large tumors with the diameter of the largest evaluable node measuring at least 3 cm.

Additionally, patients needed to be naive to BCG or discontinued the therapy more than 3 years before enrollment. Inclusion criteria also mandated local histological confirmation of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confirmed to the mucosa or submucosa; complete resection of all Ta/T1 papillary disease prior to random assignment with the most recent transurethral resection of bladder tumor occurring 2 months or less before consent to study entry was given; no prior radiotherapy to the bladder; a WHO/ECOG performance status of 0 or 1 at screening; no prior exposure to immune-mediated cancer therapy; and adequate organ and bone marrow function.

Patients were randomly assigned 1:1:1. During induction patients will receive BCG weekly for 6 weeks and undergo reinduction in the case of persistent disease, plus 13 cycles of durvalumab every 4 weeks, or BCG alone. During maintenance, patients in the durvalumab and BCG induction/maintenance and BCG-alone arms will receive another 3 weekly doses of BCG at 3, 6, 12, 18, and 24 months.

Treatment will continue for approximately 2 years in the durvalumab and BCG induction and maintenance and BCG induction/maintenance alone arms and approximately 1 year in the durvalumab and BCG induction only arm unless patients experience high-risk persistent disease or high-risk disease recurrence, disease progression, or unacceptable toxicity.

All randomized patients will be subject to survival follow-up until 5 years has passed from the date that the last patient was randomized in the study.

The primary end point is investigator-assessed DFS in the durvalumab plus BCG induction/maintenance and BCG induction/maintenance alone arms. Secondary end points include DFS in the durvalumab and BCG induction only and BCG induction/maintenance alone arms, as well as OS, time to muscle-invasive bladder cancer and/or metastatic disease, disease-related symptoms and health-related quality of life, and patient-reported outcomes.3

“The positive results for Imfinzi in the POTOMAC trial represent a significant advance that will potentially allow more patients with early-stage bladder cancer to benefit from this important immunotherapy. Building on the [phase 3] NIAGARA [NCT03732677] data, this outcome demonstrates our strategy of bringing novel therapies to patients with early-stage disease where there is the greatest potential for long-term benefit,” Cristian Massacesi, MD, chief medical officer and chief development officer of Oncology at AstraZeneca, added in the news release.1

References

1. Imfinzi regimen demonstrated statistically significant and clinically meaningful improvement in disease-free survival for high-risk non-muscle-invasive bladder cancer in POTOMAC phase III trial. News release. AstraZeneca. May 9, 2025. Accessed May 9, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-improved-dfs-in-early-bladder-cancer.html
2. De Santis M, Abdrashitov R, Hegele A, et al. A phase III, randomized, open-label, multicenter, global study of durvalumab and bacillus calmette-guérin (BCG) versus BCG alone in high-risk, BCG-naïve non-muscle-invasive bladder cancer (NMIBC) patients (POTOMAC). J Clin Oncol. 2019;37(7):TPS500. doi:10.1200/JCO.2019.37.7_suppl.TPS5
3. Assessment of efficacy and safety of durvalumab plus BCG compared to the standard therapy with BCG in non-muscle invasive bladder cancer (POTOMAC). ClinicalTrials.gov. Updated February 26, 2025. Accessed May 9, 2025. https://clinicaltrials.gov/study/NCT03528694