Durvalumab plus BCG shows consistent DFS benefit in older patients with high-risk NMIBC

A subgroup analysis of the phase 3 POTOMAC trial (NCT03528694) found that adding the PD-L1 inhibitor durvalumab (Imfinzi) in combination with BCG induction and maintenance (I+M) improved disease-free survival (DFS) among patients aged 65 years or older with high-risk, BCG-naïve non–muscle invasive bladder cancer (NMIBC).¹

The findings were presented at 41st Annual Congress of the European Association of Urology (EAU) in London, UK, by Joan Palou, MD, PhD, FEBU FRCS (Glasg), of the Universitat Autònoma de Barcelona in Spain.

POTOMAC is a randomized, open-label phase 3 trial of 1018 patients with BCG-naïve, high-risk NMIBC. Participants were randomly assigned 1:1:1 to receive durvalumab plus BCG induction and maintenance (n = 339), durvalumab plus BCG induction only (n = 339), or BCG induction and maintenance alone (n = 340).

Initial results from POTOMAC were presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany, showing that the combination of durvalumab plus BCG I+M significantly improved DFS compared with BCG I+M alone (HR, 0.68; 95% CI, 0.50 to 0.93; P = .0154).^2,3 The probability of DFS at 36 months was 82% in the combination arm vs 77% in the BCG alone arm. The previously reported data also showed no significant DFS benefit with durvalumab plus BCG induction only, highlighting the importance of maintenance therapy.

The current subgroup analysis sought to assess the combination’s safety and efficacy among older patients enrolled in the trial.

“We know that age is a prognostic factor in bladder cancer,” Palou explained during the presentation at EAU. “What we did in this sub-analysis [was] evaluate those patients above 65 years, which were 62% of the whole group.”

In this subgroup, treatment with durvalumab plus BCG I+M demonstrated a DFS benefit consistent with that observed in the overall intention-to-treat (ITT) population. Investigators reported a hazard ratio for DFS of 0.64 (95% CI, 0.44 to 0.93) in patients aged 65 years or older, comparable to the HR of 0.68 observed in the ITT population. In older patients, the DFS benefit appeared early and was sustained over time.

There also appeared to be no detriment to overall survival (OS) in older patients. OS results mirrored what was seen in the ITT population, with a HR of 0.72 (95% CI, 0.44 to 1.16) among patients aged 65 years and older and a HR of 0.80 (95% CI, 0.53 to 1.20) in the ITT population.

Safety findings in the older cohort were also consistent with those reported in the overall study population. Grade 3 or 4 adverse events (AEs) occurred in 35% of patients aged 65 and older receiving durvalumab plus BCG, compared with 34% receiving the combination in the overall study population. The rate of immune-mediated AEs among patients aged 65 years and older receiving durvalumab plus BCG was 27%, which was the same rate observed in the combination cohort in the ITT population. No treatment-related deaths were reported.

Patient-reported outcomes also suggested that adding durvalumab did not meaningfully impact quality of life. According to Palou, patient-reported GHS/QOL subscale scores did not show major deterioration during treatment (difference between arms for overall mean change from baseline, -4.2; 95% CI, -7.05 to -1.31).

“The conclusions are that 1 year of durvalumab in combination with BCG induction plus maintenance in patients aged 65 years [results in a] 36% reduction of risk of a disease-free survival event, no detriment on overall survival, and efficacy benefit consistent with the whole group,” Palou concluded during the presentation. “There has been no major impact on patient reported quality of life. This analysis further supports 1 year of durvalumab in combination with BCG induction plus maintenance as a potential new treatment for patients with BCG-naïve, high risk non-muscle invasive bladder cancer."

Editor’s note: Palou reports disclosures with AstraZeneca, Fidia, Jemedis, Olympus, and Pfizer.

REFERENCES

1. Palou J, Nishiyama H, Shore N, et al. Durvalumab (D) in combination with Bacillus Calmette-Guérin (BCG) Induction (I) and Maintenance (M) therapy for BCG-naïve, high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC): Outcomes for Patients (pts) aged ≥65 years from POTOMAC. Presented at: 41st Annual Congress of the European Association of Urology. London, UK. March 13-16, 2026. Abstract A0080

2. De Santis M, Palou J, Nishiyama H, et al. Durvalumab (D) in combination with Bacillus Calmette-Guérin (BCG) for BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC): Final analysis of the phase III, open-label, randomised POTOMAC trial. Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract LBA108. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA108.html.pdf

3. 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. Published online October 17, 2025. Accessed March 16, 2026. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01897-5/abstract