ESMO 2025 POTOMAC supports add-on durvalumab for high-risk NMIBC

medwireNews: Patients with high-risk, non-muscle-invasive bladder cancer (NMIBC) benefit from the addition of 1 year of durvalumab to Bacillus Calmette-Guérin (BCG) induction and maintenance, show phase 3 trial data.

The addition “resulted in a statistically significant and clinically meaningful improvement in disease-free survival [DFS]” in these BCG-naïve patients, investigator Maria De Santis, from Charité Universitätsmedizin Berlin in Germany, told the delegates of the ESMO Congress 2025, held in Berlin.

She added that the combination “was well tolerated, with the safety profile consistent with the known safety profiles of the individual therapies.”

De Santis therefore believes that “POTOMAC supports 1 year of durvalumab with BCG induction and maintenance therapy as a potential new treatment” for this patient population.

Outlining the background to the trial, the presenter explained that the standard of care for high-risk NMIBC is transurethral resection of bladder tumor followed by BCG induction and maintenance.

“However, there remains an unmet medical need, since despite high initial response rates with BCG therapy, approximately 40% of patients experience early recurrence or progression within 2 years,” she continued.

To evaluate whether adding durvalumab could improve outcomes, the researchers recruited 1018 BCG-naïve patients with high-risk disease, defined as any of the following; T1; high-grade or grade 3; carcinoma in situ; or multiple and recurrent and large tumors (≥3 cm).

The participants were randomly assigned to receive up to 13 cycles of durvalumab 1500 mg every 4 weeks alongside BCG induction and maintenance (n=339), the same durvalumab regimen alongside BCG induction alone (n=339), or just BCG induction and maintenance (n=340) as the control.

As reported in a simultaneous publication in The Lancet, the trial met its primary endpoint, showing a significant 32% reduction in the risk for recurrence or death with the addition of durvalumab to BCG induction and maintenance versus just BCG induction and maintenance.

At a median follow-up of 60.7 months, the median DFS durations were unreached in the durvalumab plus BCG induction and maintenance, and control arms, but the 1-, 2-, and 3-year DFS rates were 92% versus 87%, 87% versus 82%, and 82% versus 77%, respectively.

“There was an early separation of the Kaplan–Meier curves, starting at less than 4 months, with the curves remaining separated throughout,” noted the presenter.

She further highlighted that although the study was not powered to assess overall survival, a descriptive analysis showed “no detriment” with the addition of the PD-L1 inhibitor.

Of note, there was no significant difference in DFS between the durvalumab plus BCG induction-only arm and the BCG induction and maintenance arm.

With regard to safety, adverse events (AEs) of grade 3 or 4 that were possibly related to any treatment were more frequent when durvalumab was added to BCG induction and maintenance or to BCG induction alone, at respective rates of 21% and 15% versus 4% without durvalumab.

The corresponding rates of grade 3–4 immune-mediated AEs were 8.0%, 8.0%, and 0.3%. And there were no deaths due to treatment-related AEs in any group.

Discussant Bradley McGregor (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) highlighted, however, that immune-mediated AEs in particular can often be life altering, and therefore it is important to weigh toxicities – both short- and long-term – with the degree of benefit and potential for salvage therapies.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature

ESMO Congress 2025; Berlin, Germany: 17–21 October
Lancet 2025; doi:10.1016/S0140-6736(25)01897-5