POTOMAC: Durvalumab plus BCG boosts disease-free survival in NMIBC

Final results of the phase 3 POTOMAC study (NCT03528694) indicate that combining durvalumab (Imfinzi) with BCG induction and maintenance for the treatment of BCG-naïve, high-risk non–muscle invasive bladder cancer (NMIBC) is associated with statistically significant and clinically meaningful improvement in disease-free survival (DFS).¹

Maria De Santis, MD, of Charité - Universitätsmedizin Berlin in Berlin, Germany, presented the findings at the 2025 European Society for Medical Oncology Congress in Berlin. The data were simultaneously published in The Lancet.² Introducing her presentation, De Santis commented that the combination of durvalumab and BCG could result in improved outcomes for patients with BCG-naïve, high-risk NMIBC.

The randomized, open-label phase 3 POTOMAC study included adult patients with BCG-naïve NMIBC with high-risk tumor as defined by T1, high-grade/G3, carcinoma in situ, or multiple and recurrent and large (3 cm or larger). Patients were randomly assigned 1:1:1 to receive durvalumab 1500 mg intravenously every 4 weeks for 13 cycles plus BCG induction and maintenance, durvalumab 1500 mg intravenously every 4 weeks for 13 cycles plus BCG induction only, or BCG induction and maintenance. The primary end point was investigator-assessed DFS for the durvalumab/BCG induction and maintenance arm vs the BCG-only arm. Key secondary end points included DFS for the durvalumab/BCG induction only arm vs the BCG-only arm, DFS at 24 months, and complete response rate at 6 months. Other secondary end points included overall survival (OS) at 5 years, safety, and EORTC QLQ-C30.

A total of 1350 patients were enrolled, and 1018 patients were randomly assigned: 339 patients were assigned to the durvalumab/BCG induction and maintenance group, 339 were assigned to the durvalumab/BCG induction only arm, and 340 were assigned to the BCG-only arm.

“At the time of the data cut-off, all the patients were off study treatment, and more than half in each arm completed treatment,” De Santis said.

De Santis reported a high rate of compliance with BCG treatment, with a median 14.0 maintenance instillations administered in both the durvalumab/BCG induction and maintenance arm and the BCG-only arm. In addition, 181 (54%) patients in the durvalumab/BCG induction and maintenance arm had a BCG cumulative exposure of at least 18 months, and 208 (61%) patients in the BCG-only arm had a BCG cumulative exposure of at least 18 months.

“POTOMAC met its primary end point of disease-free survival in the ITT [intent-to-treat] population…Compared with the control arm, durvalumab in combination with BCG induction and maintenance demonstrated a statistically significant DFS benefit, with a hazard ratio of 0.68 and a P value of 0.0154,” De Santis reported.

De Santis noted that although the study was not powered to assess OS, a descriptive analysis conducted by the investigators found no detriment to OS when adding durvalumab to BCG induction and maintenance (HR, 0.80: 95% CI: 0.53-1.20).

The investigators assessed quality of life at baseline and then every 8 weeks using the EORTC QLQ-C30. This “showed that the addition of durvalumab to BCG induction and maintenance treatment had no major impact on patient-reported quality of life,” De Santis said.

Regarding the key secondary end point of DFS in the durvalumab/BCG induction only arm vs the BCG-only arm found that the difference in DFS between the groups was not statistically significant (HR, 1.14, 95% CI: 0.86-1.50, P = .03530).

Treatment with durvalumab/BCG induction and maintenance was found to be tolerable and manageable, according to De Santis. She noted that although adverse events (AEs) of any cause, maximum grade 3 or 4 AEs, serious AEs, AEs leading to death, and AEs leading to discontinuation of study treatment were all higher in the durvalumab/BCG induction and maintenance arm, there were no treatment-related AEs that led to death in any of the treatment arms. The most commonly reported AEs included dysuria, hematuria, pollakiuria, urinary tract infection, cystitis, pyrexia, arthralgia, hypothyroidism, fatigue, diarrhea, rash, constipation, and increased lipase.

“In conclusion, the addition of 1 year of durvalumab to BCG induction and maintenance therapy resulted in a statistically significant and clinically meaningful improvement in disease-free survival in patients with BCG-naïve, high-risk NMIBC. After a median follow-up of approximately 5 years, a 32% risk reduction of a DFS event occurring with the addition of durvalumab to BCG induction and maintenance therapy was observed…POTOMAC supports 1 year of durvalumab with BCG induction and maintenance therapy as a potential new treatment in BCG-naïve, high-risk NMIBC,” De Santis said.

DISCLOSURES: De Santis listed consulting fee/honoraria/support for attending meetings and/or travel/participation on safety monitoring board or advisory board/leadership or fiduciary role for AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, Bristol Myers Squibb, Eisai, Ferring, Gilead Sciences, Immunomedics, Ipsen, Janssen, Merck Sharp & Dohme, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, SeaGen, and Thermosome.

REFERENCES

1. 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

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. Published online October 17, 2025. Accessed October 18, 2025. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01897-5/abstract