AstraZeneca’s Phase III POTOMAC Trial Shows Imfinzi Significantly Improves Disease-Free Survival in High-Risk NMIBC

AstraZeneca has shared new data from the Phase III POTOMAC clinical trial (NCT03528694) evaluating Imfinzi (durvalumab) among participants with Bacillus Calmette-Guérin (BCG)-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC).¹

Imfinzi plus BCG therapy significantly improves disease-free survival

Breaking POTOMAC results from the European Society for Medical Oncology (ESMO) Congress 2025 show that adding one year of treatment with Imfinzi to BCG induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared to BCG induction alone.

Detailed findings from POTOMAC show:

• After a median follow-up of 60.7 months, the Imfinzi regimen reduced the risk of high-risk disease recurrence or death by 32% versus the comparator (hazard ratio [HR] 0.68; 95% CI: 0.50–0.93; P=0.0154).
• Median DFS was not yet reached in either treatment arm.
• At two years, 87% of patients receiving the Imfinzi regimen remained alive and disease-free compared with 82% in the comparator arm.
• Overall survival (OS) was not formally powered for analysis, but a descriptive assessment after 65.6 months showed an OS HR of 0.80 (95% CI: 0.53–1.20), indicating no survival detriment.

In a press release, Maria De Santis, MD, head of the Interdisciplinary Uro-Oncology Section at Charité – Universitätsmedizin Berlin, Germany, and a principal investigator in the POTOMAC trial, said: “While patients with early-stage bladder cancer are treated with the goal of cure, early recurrence is common among those with high-risk non-muscle-invasive bladder cancer. This can lead to repeated surgical procedures and more intensive treatment, including removing a patient’s bladder which deeply affects their quality of life. The results of POTOMAC showed that adding one year of durvalumab to BCG bladder instillation treatment reduced the risk of recurrence by 32%, allowing more patients to remain disease-free and alive at two years.”

Trial design and endpoints

POTOMAC is a global, randomized, open-label, multicenter trial evaluating Imfinzi in combination with BCG therapy in 1,018 patients with BCG-naïve, high-risk NMIBC.

• Patients were randomized 1:1:1 to receive Imfinzi plus BCG induction and maintenance therapy, Imfinzi plus BCG induction only, or BCG induction and maintenance therapy alone.
• BCG induction therapy was administered for six weeks, with or without two years of maintenance.
• The primary endpoint was DFS for Imfinzi plus BCG induction and maintenance versus BCG alone; secondary endpoints included DFS for the induction-only arm, five-year OS, and safety.
• The trial enrolled participants across more than 120 sites in 12 countries, with median follow-up for DFS exceeding five years, marking it as one of the longest among NMIBC studies.

In the press release, Susan Galbraith, executive vice president, oncology hematology R&D, AstraZeneca, added: “The early and sustained disease-free survival benefit observed in the POTOMAC trial demonstrates Imfinzi has the potential to change the course of high-risk non-muscle-invasive bladder cancer by extending the time patients live without high-risk disease recurrence or progression. These results build on Imfinzi’s practice-changing impact in muscle-invasive bladder cancer and further validate our strategy to bring novel therapies into earlier-stage disease where they can have the greatest impact on patients’ lives.”

Building on prior success in muscle-invasive bladder cancer

In September 2024, Imfinzi (durvalumab) became the first immunotherapy regimen to significantly extend OS in patients with muscle-invasive bladder cancer. In addition to improvements in OS, Phase III NIAGARA trial (NCT03732677) results from the time showed that Imfinzi in combination with chemotherapy significantly improved event-free survival (EFS) compared to neoadjuvant chemotherapy.²

Detailed results from this readout of NIAGARA showed:

• At 24 months, estimated EFS was 67.8% (95% CI: 63.6–71.7) with Imfinzi versus 59.8% (95% CI: 55.4–64.0) in the comparison cohort.
• The Imfinzi regimen reduced the risk of progression, recurrence, failure to undergo radical cystectomy, or death by 32% (HR 0.68; 95% CI: 0.56–0.82; P<0.001).
• Estimated OS at 24 months was 82.2% (95% CI: 78.7–85.2) with Imfinzi versus 75.2% (95% CI: 71.3–78.8) in the comparator arm.
• The risk of death was reduced by 25% in the Imfinzi group (HR 0.75; 95% CI: 0.59–0.93; P=0.01).

References

1. IMFINZI® (durvalumab) regimen reduced the risk of disease recurrence or death by 32% in high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial. News release. AstraZeneca. October 17, 2025. Accessed October 20, 2025. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2025/IMFINZI-durvalumab-regimen-reduced-the-risk-of-disease-recurrence-or-death-by-32-percent-in-high-risk-non-muscle-invasive-bladder-cancer-in-the-POTOMAC-Phase-III-trial.html

2. Imfinzi Treatment Regimen Shows Promise for Muscle-Invasive Bladder Cancer. Applied Clinical Trials. September 19, 2024. Accessed October 20, 2025. https://www.appliedclinicaltrialsonline.com/view/imfinzi-treatment-regimen-promise-muscle-invasive-bladder-cancer