FDA Approves Durvalumab Plus BCG for High-Risk Non–Muscle Invasive Bladder Cancer

The FDA has approved durvalumab (Imfinzi; AstraZeneca) in combination with BCG for the treatment of adult patients with BCG-naive, high-risk non–muscle invasive bladder cancer (NMIBC). The approval introduces a new frontline treatment option for patients with high-risk disease following transurethral resection of bladder tumor (TURBT).¹

The agency based its approval on findings from the phase 3 POTOMAC trial (NCT03528694), which evaluated durvalumab in combination with BCG induction and maintenance therapy in patients with BCG-naive, high-risk NMIBC.² High-risk NMIBC was defined as the presence of T1 tumors, grade 3 or high-grade tumors, carcinoma in situ (CIS), or multiple, recurrent, and large tumors.¹

Study Findings

In the randomized, open-label, multicenter study, investigators enrolled 1018 patients following TURBT. Patients were randomly assigned 1:1:1 to receive one of the following regimens: durvalumab every 4 weeks for 13 cycles plus BCG induction and maintenance therapy; durvalumab plus BCG induction only; or BCG induction and maintenance alone.^1,2

The primary end point was investigator-assessed disease-free survival (DFS), defined as the time from randomization to recurrence of high-risk NMIBC, persistent CIS, muscle-invasive bladder cancer, metastatic disease, or death.¹

At a median follow-up of 60.7 months, investigators observed a statistically significant improvement in DFS among patients receiving durvalumab plus BCG induction and maintenance compared with BCG alone. The combination reduced the risk of recurrence of high-risk disease or death by approximately 32% (HR, 0.68; 95% CI, 0.50-0.93; P = .015).² Median DFS was not reached in either treatment arm at the time of analysis.¹

Investigators reported 67 DFS events in the durvalumab plus BCG induction and maintenance group compared with 98 events in the BCG-alone group. According to the study authors, the findings demonstrated a clinically meaningful benefit of adding immune checkpoint inhibition to standard BCG therapy in this setting.²

“Among patients with BCG-naive, high-risk NMIBC, 1 year of durvalumab combined with BCG induction and maintenance therapy showed a statistically significant and clinically meaningful improvement in DFS vs BCG induction and maintenance alone,” the investigators wrote.²

Safety findings were generally consistent with the known profiles of durvalumab and BCG. Grade 3 or 4 treatment-related adverse events occurred in approximately 21% of patients receiving durvalumab plus BCG induction and maintenance, compared with 4% of patients receiving BCG alone. No treatment-related deaths were reported.²

The prescribing information for durvalumab includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.¹

The recommended dose of durvalumab for patients weighing at least 30 kg is 1500 mg intravenously every 4 weeks for up to 13 cycles in combination with BCG induction and maintenance therapy. Treatment should continue until recurrence of high-risk disease, progression, unacceptable toxicity, or completion of the maximum 13 cycles.¹

According to the FDA, the application underwent standard review and used the agency’s Assessment Aid program, a voluntary submission process to facilitate regulatory review.¹

REFERENCES

1. FDA approves durvalumab in combination with Bacillus Calmette-Guerin for high-risk non-muscle invasive bladder cancer. FDA. May 28, 2026. Accessed May 28, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-combination-bacillus-calmette-guerin-high-risk-non-muscle-invasive-bladder

2. De Santis M, Palou Redorta J, Nishiyama H, et al; POTOMAC Investigators. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Lancet. 2025;406(10516):2221-2234. doi:10.1016/S0140-6736(25)01897-5