FDA Approves Durvalumab Plus BCG for High-Risk NMIBC

The FDA has approved durvalumab (Imfinzi) for use in combination with Bacillus Calmette-Guerin (BCG) for the treatment of adult patients with BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC).¹

The approval was supported by the phase 3 POTOMAC trial (NCT03528694). The latest findings from the study were shared at the 2026 American Urological Association Annual Meeting² and showed that compared with BCG induction and maintenance alone, a regimen that added durvalumab to that regimen reduced the risk of disease recurrence or death by 32% (HR, 0.68; 95% CI, 0.50-0.93; P =.0154) at a median follow-up of 60.7 months and 24% DFS maturity, with 67 events (20%) in the durvalumab-plus-BCG induction-maintenance (D+BCG I+M) arm vs 98 events (29%) in the BCG induction-maintenance (BCG I+M) arm; median DFS was not reached in either arm.²

POTOMAC Study Rationale and Design

In patients with high-risk NMIBC, including those with high-grade Ta, T1, and carcinoma in situ disease, early recurrence following BCG induction-maintenance carries significant clinical consequences, with BCG-unresponsive disease representing an indication for radical cystectomy per international guidelines.^2,3 Despite BCG remaining the standard of care for more than 3 decades, approximately 40% of patients experience early recurrence or progression within 2 years, and adherence to the recommended 2 to 3 years of maintenance BCG remains low in routine practice.³ Papillary tumors constitute the majority of NMIBC diagnoses, and outcomes for patients with papillary stage T1 and high-grade tumors treated with standard BCG induction-maintenance remain poor.³

Durvalumab, a PD-L1 inhibitor, was evaluated in combination with BCG induction-maintenance on the basis that immune checkpoint blockade may enhance the antitumor immune response initiated by BCG, potentially reducing early recurrence, BCG-unresponsive disease, and the downstream need for cystectomy.² The originally reported POTOMAC results, published in The Lancet, demonstrated a statistically significant DFS benefit with D+BCG I+M vs BCG I+M alone.^2,3 The analyses presented at the 2026 AUA Annual Meeting include expanded efficacy, subgroup, and safety outcomes not previously reported.²

In the phase 3 POTOMAC trial, 1,018 patients with BCG-naive, high-risk NMIBC who had undergone complete transurethral resection of bladder tumor were randomized 1:1:1 to D+BCG I+M (n = 339), durvalumab with BCG induction only (n = 339), or BCG I+M alone (n = 340).^2,3 The primary end point was DFS. Key secondary end points included overall survival (OS) and time to cystectomy. Data cutoff was April 3, 2025, with enrollment spanning June 2018 to October 2020.²

Updated Efficacy Outcomes

In an analysis of early high-risk disease events within the first year, 53 patients (16%) in the D+BCG I+M arm experienced a high-risk event vs 69 (20%) in the BCG I+M arm. Among those who experienced an event, the median time to event was 14.1 months vs 8.3 months, respectively, and the proportion with an event within 12 months was 45% (n = 24 of 53) vs 61% (n = 42 of 69). The addition of durvalumab did not compromise patients’ ability to receive adequate BCG therapy: 87% (n = 291 of 336) in the D+BCG I+M arm vs 93% (n = 315 of 339) in the BCG I+M arm completed an adequate BCG course.

Among patients who developed high-risk NMIBC recurrence or persistent CIS, BCG-unresponsive disease occurred in 65% (n = 24 of 37) of D+BCG I+M patients vs 81% (n = 44 of 54) of BCG I+M patients. In that BCG-unresponsive subset, 8% (n = 2 of 24) proceeded to cystectomy in the D+BCG I+M arm vs 25% (n = 11 of 44) in the BCG I+M arm. In the ITT population, cystectomy events numbered 13 (4%) vs 21 (6%) (HR, 0.63; 95% CI, 0.31-1.24), with a median time to procedure of 19.0 months vs 14.1 months among those who underwent cystectomy. An analysis of cystectomy-free survival showed 49 events (14%) vs 70 events (21%; HR, 0.69; 95% CI, 0.48-0.99); median cystectomy-free survival was not reached in either arm.

In the papillary-only population (64% to 65% of the ITT population; D+BCG I+M n = 217; BCG I+M n = 220), 37 DFS events (17%) vs 65 events (30%) occurred (HR, 0.56; 95% CI, 0.37-0.84; P = .0046). Among patients with any papillary tumors, the HR was 0.61 (95% CI, 0.43-0.84); the T1-only subgroup yielded an HR of 0.48 (95% CI, 0.28-0.79), and the T1 HG/G3-only subgroup an HR of 0.55 (95% CI, 0.31-0.95). OS, with a median follow-up of 65.6 months and 14% maturity, showed no detriment with durvalumab: 41 deaths (12%) vs 52 deaths (15%) in the BCG I+M arm (HR, 0.80; 95% CI, 0.53-1.20), with OS trends across papillary subgroups consistent with the intention-to-treat (ITT) population finding.

Safety Profile of Durvalumab Plus BCG in POTOMAC

In the overall safety population (D+BCG I+M n = 336, BCG I+M n = 339), any-cause adverse effects (AEs) occurred in 97% vs 91% of patients, respectively. Treatment-related grade 3 or 4 adverse effects (AEs) occurred in 21% vs 4%, serious AEs possibly related to any treatment in 13% vs 4%, and AEs leading to discontinuation in 31% vs 20%; discontinuations possibly related to durvalumab specifically were 16% vs 0.3%. No treatment-related deaths occurred in either arm.

Immune-mediated AEs (imAEs) of any grade occurred in 27% (n = 91 of 336) of D+BCG I+M patients vs 1% (n = 4 of 339) in the BCG I+M arm. Grade 3 or 4 imAEs occurred in 8% (n = 27 of 336), and imAEs leading to treatment discontinuation in 10% (n = 32 of 336). The most common imAEs were hypothyroid events (11%), hepatic events (5%), dermatitis/rash (3%), hyperthyroid events (2%), and thyroiditis (2%); the majority were low grade and manageable. Of the 91 patients with imAEs, 47% (n = 43 of 91) had fully resolved events, 16% (n = 15 of 91) were still resolving, 3% (n = 3 of 91) resolved with sequelae, and 33% (n = 30 of 91) had not resolved at data cutoff. The safety profile in the papillary-only subgroup was consistent with that of the overall population.

REFERENCES

1. US Food and Drug Administration. FDA approves durvalumab in combination with Bacillus Calmette-Guerin for high-risk non-muscle invasive bladder cancer. 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. Shore ND, Nishiyama H, Palou Redorta J, et al. Durvalumab in combination with BCG induction and maintenance therapy for BCG-naive, high-risk non–muscle-invasive bladder cancer: expanded efficacy and safety analyses from POTOMAC. Presented at: 2026 American Urological Association Annual Meeting; May 15-18, 2026; Washington, DC.

3. 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;406:2221-2234. doi:10.1016/S0140-6736(25)01897-5