Durvalumab Combo Demonstrates DFS Improvement in High-Risk NMIBC

The POTOMAC trial evaluating durvalumab plus BCG in high-risk NMIBC was not statistically powered to test overall survival, but a descriptive analysis showed no detriment with durvalumab.

After one year of treatment, durvalumab (Imfinzi) plus Bacillus Calmette-Guérin (BCG) induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) vs BCG therapy alone in patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC) who had undergone prior transurethral resection of bladder tumor (TURBT), according to a news release on data from the phase 3 POTOMAC trial (NCT03528694).¹

The POTOMAC trial evaluating durvalumab plus BCG in high-risk NMIBC was not statistically powered to test overall survival (OS), but a descriptive analysis showed no detriment with durvalumab. Additionally, durvalumab plus BCG induction and maintenance therapy were considered safe and well-tolerated, demonstrating consistency with the known profiles of individual agents, and no new safety signals were identified. Furthermore, the ability for patients to undergo BCG induction and maintenance therapy was not compromised with durvalumab treatment.

A second experimental arm evaluating durvalumab plus BCG induction without the inclusion of maintenance therapy vs BCG induction and maintenance alone did not elicit statistically significant DFS outcomes. Additionally, these results will be presented at a future medical meeting and shared with global regulatory authorities.

“These exciting data show that adding 1 year of durvalumab to the current standard treatment significantly extends the time patients live without high-risk disease recurrence or progression,” principal investigator Maria De Santis, MD, head of the Interdisciplinary Uro-Oncology Section at Charité Universitätsmedizin in Berlin, Germany, said in the news release.¹ “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."

Patients in the phase 3 trial (n = 1018) were randomly assigned 1:1:1 to receive durvalumab plus BCG induction and maintenance therapy, durvalumab plus BCG induction only, or BCG standard-of-care induction plus maintenance.² The primary end point was DFS in the durvalumab/BCG induction/maintenance arm. Secondary end points included DFS in the BCG induction only arm, 5-year OS, and safety.

Patients were eligible for trial enrollment if they were 18 years and older, had no prior BCG, and had histological confirmation of high-risk translational cell carcinoma of the urinary bladder confined to the mucosa or submucosa.² Additional eligibility criteria included complete resection of all Ta/T1 papillary disease at 4 or fewer months before random assignment; no prior bladder cancer-related radiotherapy; and no previous exposure to immune-mediated anticancer therapy, including anticancer vaccines.

Those ineligible for enrollment had evidence of muscle-invasive, locally advanced, metastatic, and/or vesical bladder cancer; concurrent extravesical, non-muscle-invasive transitional cell carcinoma of the urothelium; or previous investigational product (IP) assignment in the present study. Additional exclusion criteria included concurrent chemotherapy, IP, or biologic/hormonal anticancer therapy; active or previously documented autoimmune or inflammatory disorders; and a history of another primary malignancy, excluding malignancies treated with curative intent and no known active disease at least 2 years before first IP dose and of low potential risk for recurrence during study period.

“The positive results for [durvalumab] 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,” Cristian Massacesi, chief medical officer and oncology chief development officer at AstraZeneca, the developer of durvalumab, said in the news release.¹ “Building on the 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.”

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. May 9, 2025. Accessed May 9, 2025. https://tinyurl.com/bdza82hm
2. 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://tinyurl.com/43bmn623