Durvalumab plus BCG improves DFS in papillary-only, BCG-naïve NMIBC

Adding 1 year of durvalumab (Imfinzi) to BCG induction and maintenance reduced the risk of high-risk disease recurrence or death by 44% compared with BCG induction and maintenance alone in patients with BCG-naïve, high-risk, papillary-only non–muscle invasive bladder cancer (NMIBC), according to a subgroup analysis of the phase 3 POTOMAC trial (NCT03528694) presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain.¹

The data follow the FDA's May 2026 approval of durvalumab plus BCG for BCG-naïve, high-risk NMIBC. The current analysis specifically focused on patients with papillary-only disease.

"Papillary-only tumors are a major subgroup of high-risk NMIBC, with substantial risk of recurrence and progression, high unmet need, [and] few established bladder-sparing options after BCG failure," said presenting author Maria De Santis, MD, of Charité Universitätsmedizin Berlin, Germany, during the presentation at ESMO.

Trial overview

The open-label POTOMAC trial (NCT03528694) randomly assigned 1018 patients with BCG-naive, high-risk NMIBC 1:1:1 to durvalumab 1500 mg intravenously every 4 weeks for 13 cycles plus BCG induction and maintenance (I+M); durvalumab plus BCG induction only; or BCG I+M alone. In the final analysis, published in The Lancet, the durvalumab plus BCG I+M arm met the primary end point of investigator-assessed disease-free survival (DFS) vs BCG I+M alone at a median follow-up of 60.7 months (HR, 0.68; 95% CI, 0.50 to 0.93; P = .0154). Durvalumab plus BCG induction alone did not improve DFS compared with BCG induction and maintenance (HR, 1.14; 95% CI, 0.86 to 1.50; P = .35).²

The ESMO analysis focused on patients with papillary-only tumors, which included 217 patients in the durvalumab arm and 220 in the BCG arm, or 64% to 65% of the ITT population. Median age was 67 years in both arms, 63% and 66% of patients had T1 disease, and 53% and 55% had higher-risk papillary disease, respectively.

Efficacy and safety data

DFS events occurred in 17% of papillary-only patients in the durvalumab arm vs 30% in the BCG arm (HR, 0.56; 95% CI, 0.37 to 0.84), with 48-month DFS rates of 84% vs 74%, respectively. In the T1 subset (137 vs 145 patients), event rates were 16% vs 31% (HR, 0.48; 95% CI, 0.28 to 0.79), and 48-month DFS rates were 85% vs 73%. Median DFS was not reached in either arm of either group.

High-risk disease recurrence occurred in 13% vs 20% of papillary-only patients. The difference was confined to high-risk NMIBC recurrence (8% vs 15%). Progression to muscle-invasive bladder cancer (MIBC) or metastatic disease occurred in 5% of each arm. In the T1 subset, high-risk disease recurrence occurred in 12% of patients in the durvalumab plus BCG I+M arm vs 22% of patients in the BCG I+M alone arm.

Early high-risk events, those within 12 months of randomization, occurred in 16 vs 29 patients overall and in 10 vs 20 patients with T1 disease. Among patients with a high-risk NMIBC recurrence, 61.1% (11 of 18) in the durvalumab arm met BCG-unresponsive criteria vs 88.2% (30 of 34) in the BCG arm. In the T1 subset, these rates were 60% and 87.5%, respectively.

Cystectomy was performed in 6 patients (3%) receiving durvalumab plus BCG vs 12 patients (5%) receiving BCG alone, and in 4 (3%) vs 9 (6%) patients with T1 disease. Cystectomy-free survival, defined as time to cystectomy or death from any cause, favored the combination in the papillary-only group (HR, 0.59; 95% CI, 0.38 to 0.92) and the T1 subset (HR, 0.45; 95% CI, 0.25 to 0.78).

Safety in the papillary-only population mirrored the overall safety population. Grade 3 or 4 adverse events (AEs) occurred in 34% of patients receiving durvalumab plus BCG vs 16% receiving BCG alone, including treatment-related grade 3 or 4 AEs in 23% vs 3%. Serious AEs occurred in 30% vs 17%, and AEs led to treatment discontinuation in 29% vs 17%. No deaths were attributed to treatment.

Immune-mediated AEs occurred in 27% of the durvalumab arm (grade 3 or 4 in 9%). Most common immune-mediated AEs included hypothyroid events (11%) and hepatic events (7%). At data cutoff, 40% of patients with immune-mediated AEs had events that had not resolved.

“The addition of durva[lumab] to BCG led to fewer early high-risk disease recurrences, fewer BCG unresponsive recurrences, and favorable cystectomy-related outcomes,” De Santis concluded during the presentation. “These findings further support 1 year of durvalumab in combination with BCG induction and maintenance as a new treatment option for BCG-naïve, high-risk NMIBC, including those patients with papillary-only tumors.”

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REFERENCES

1. De Santis M, Shore ND, Palou J, et al. Durvalumab (D) in combination with BCG induction and maintenance (I+M) for BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC): Early recurrence and cystectomy-free survival in patients (pts) with papillary only tumours from POTOMAC. Presented at: 2026 European Society for Medical Oncology Congress. October 23-27, 2026. Madrid, Spain. Abstract 4737RO. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2026_abstracts/4737RO.html.pdf

2. De Santis M, Redorta JP, Nishiyama H, et al. 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