FDA Approves Durvalumab Plus BCG for High-Risk NMIBC

The FDA has approved durvalumab (Imfinzi) in combination with BCG for the treatment of adult patients with BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC).

The regulatory decision was supported by data from the phase 3 POTOMAC trial (NCT03528694), which demonstrated that treatment with durvalumab plus BCG induction and maintenance (n = 339) led to a statistically significant improvement in disease-free survival (DFS) compared with BCG induction and maintenance alone (n = 340; HR, 0.68; 95% CI, 0.50-0.93; P = .0154).^1,2 The median DFS was not reached in both arms of the study.

For patients with BCG-naive, high-risk NMIBC weighing at least 30 kg, durvalumab is recommended at 1500 mg every 4 weeks for 13 cycles in combination with BCG induction and maintenance. Treatment should continue until recurrence of high-risk disease, disease progression, unacceptable toxicity, or a maximum of 13 cycles.

How was the POTOMAC trial designed?

The open-label, randomized, phase 3 study enrolled patients at least 18 years of age with BCG-naive NMIBC.² Patients needed to have high-risk tumors, defined as at least 1 of the following factors:

• T1 disease
• high-grade/grade 3 disease
• carcinoma in situ (CIS)
• multiple, recurrent, and large (≥3 cm) disease

Patients were randomly assigned 1:1:1 to receive durvalumab plus BCG induction and maintenance; durvalumab plus BCG induction only; or BCG induction and maintenance alone. Patients were stratified by higher-risk papillary disease (yes vs no) and CIS (yes vs no).

In both durvalumab-containing arms, the agent was administered at 1500 mg once every 4 weeks for 13 cycles. All patients received BCG induction once per week for 6 weeks, and in the 2 arms with BCG maintenance, treatment was given as 3 weekly doses at 3 months, 6 months, 12 months, 18 months, and 24 months.

DFS for durvalumab plus BCG induction/maintenance vs BCG induction/maintenance alone served as the trial’s primary end point. Secondary end points included DFS for durvalumab plus BCG induction alone vs BCG induction/maintenance alone; DFS rate at 24 months; complete response rate at 6 months; overall survival at 5 years; safety; and quality of life.

What additional efficacy data have been reported from POTOMAC?

Findings from the study’s final analysis presented at the 2025 ESMO Congress showed that patients treated with durvalumab plus BCG induction/maintenance experienced 12-, 24-, and 36-month DFS rates of 92%, 87%, and 82%, respectively. In patients treated with BCG induction/maintenance alone, these respective rates were 87%, 82%, and 77%.

With data at 14% maturity, the median OS was not reached in the durvalumab plus BCG induction/maintenance arm and the BCG induction/maintenance alone arm at median follow-ups of 65.6 months and 65.9 months, respectively (HR, 0.80; 95% CI, 0.53-1.20).

Notably, a statistically significant difference in DFS was not observed for durvalumab plus BCG induction alone vs BCG induction/maintenance alone (HR, 1.14; 95% CI, 0.86-1.50; P = .3530).

What was reported regarding safety for durvalumab plus BCG induction/maintenance?

Any-grade adverse effects (AEs) occurred in 97% of patients treated with durvalumab plus BCG induction/maintenance (n = 336) vs 91% of patients given BCG induction/maintenance alone (n = 339). The rates of any-grade AEs deemed possibly related to any treatment were 89% and 72%, respectively. The rates of grade 3/4 AEs were 34% for durvalumab plus BCG induction/maintenance vs 17% for BCG induction/maintenance alone; the resepctive rates of these AEs deemed possibly related to treatment were 21% and 4%. Serious AEs occurred at rates of 32% and 19%, respectively.

AEs led to death in 2% of patients in the experimental arm vs 1% of patients in the control arm; no deaths were deemed possibly related to treatment during the study.

In the durvalumab plus BCG induction/maintenance group, AEs led to treatment discontinuation in 31% of patients compared with 20% for BCG induction/maintenance alone.

The most common any-grade AEs included dysuria (durvalumab plus BCG induction/maintenance, 37%; BCG induction/maintenance alone, 36%), hematuria (32%; 30%), pollakluria (26%; 25%), urinary tract infection (21%; 18%), cystitis (19%; 19%), pyrexia (16%; 20%), arthralgia (13%; 6%), hypothyroidism (13%; 0%), fatigue (12%; 6%), diarrhea (15%; 6%), rash (12%; 3%), constipation (11%; 5%), and increased lipase levels (10%; 3%).

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. Durvalumab (D) in Combination With Bacillus Calmette-Guerin (BCG) for BCG-Naive, High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC): Final Analysis of the Phase 3, Open-Label, Randomized POTOMAC Trial. Presented at: 2025 ESMO Congress; October 17-20, 2025; Berlin, Germany. Abstract LBA108.