POTOMAC phase 3 trial: durvalumab plus BCG reduced the risk of recurrence or death by 32% (HR 0.68) in BCG-naive high-risk NMIBC. FDA approval on 28 May 2026.
Expanded analyses of the phase 3 POTOMAC trial were presented at the AUA 2026 Congress and confirmed a 32% reduction in the risk of recurrence or death
19 July 2026 | Source: FDA, The Lancet, Urology Times, OncLive, UroToday, AJMC, AstraZeneca | Topic: Bladder Cancer / Uro-Oncology
KEY FINDINGS
- FDA approval: On 28 May 2026 the FDA approved durvalumab (Imfinzi®) plus BCG for BCG-naive high-risk non-muscle-invasive bladder cancer (NMIBC) - the first immunotherapy-BCG combination regimen approved in this indication.
- Efficacy: In the phase 3 POTOMAC trial, durvalumab plus BCG induction/maintenance produced a 32% risk reduction in disease-free survival compared with BCG alone (HR 0.68; 95% CI 0.50-0.93; p=0.0154).
- Expanded analysis: Analyses presented at the AUA 2026 congress showed a reduction in early recurrences and a decrease in rates of BCG-unresponsive recurrence.
- Safety: The safety profile was found to be manageable; no meaningful deterioration in patients' quality of life was detected.
Study Design and Background
Although BCG (Bacillus Calmette-Guérin) immunotherapy has been the standard of care in high-risk non-muscle-invasive bladder cancer (NMIBC) for decades, a substantial proportion of patients experience recurrence or progression. The POTOMAC trial (NCT03528694) is a randomized, open-label, international phase 3 study designed to close this treatment gap.
A total of 1,018 patients with BCG-naive, high-risk NMIBC were enrolled and randomized 1:1:1 to three arms: durvalumab 1,500 mg IV (every 4 weeks, 13 cycles) plus BCG induction and maintenance (n=339), durvalumab plus BCG induction only (n=339), and BCG induction/maintenance alone (n=340, control arm). The primary endpoint was disease-free survival (DFS).
Key Results
In the analysis performed at a median follow-up of 60.7 months and 24% DFS maturity, 67 events (20%) occurred in the durvalumab plus BCG induction/maintenance arm versus 98 events (29%) in the control arm. This difference corresponds to a statistically significant reduction in the risk of disease recurrence or death.
| Parameter | Value |
|---|---|
| Reduction in risk of recurrence/death (durvalumab + BCG maintenance arm) | 32% |
| Hazard ratio (HR) | 0.68 (95% CI 0.50-0.93) |
| Total number of patients randomized | 1,018 |
| Median follow-up | 60.7 months |
| Treatment Arm | Number of Patients | DFS Events | Grade 3-4 Treatment-Related Adverse Events |
|---|---|---|---|
| Durvalumab + BCG (induction + maintenance) | 339 | 67 (20%) | 21% |
| Durvalumab + BCG (induction only) | 339 | - | 15% |
| BCG alone (control) | 340 | 98 (29%) | 4% |
In terms of safety, the most frequent immune-related adverse events were hypothyroidism (11%), hepatic events (5%), dermatitis/rash (3%) and hyperthyroidism (2%). The rate of grade 3-4 immune-related adverse events was 8%, and no treatment-related deaths were reported. Patient-reported outcome (PRO) measures of quality of life showed no meaningful difference between the arms.
Exploratory analyses presented at the AUA 2026 congress also showed that adding durvalumab reduced the number of high-risk recurrences within the first year and lowered rates of BCG-unresponsive recurrence compared with BCG alone.
Implications for Clinical Practice
FDA approval of durvalumab plus BCG in BCG-naive high-risk NMIBC has the potential to change the "BCG alone" standard that has prevailed in this patient group for decades. It may be considered as a bladder-sparing strategy particularly in patients at high risk of recurrence who wish to avoid radical cystectomy. However, the markedly higher risk of immune-related adverse events (21% grade 3-4) compared with BCG alone calls for care in patient selection and multidisciplinary follow-up (in collaboration with endocrinology and gastroenterology).
The pembrolizumab plus BCG data presented at the same congress (a 92% complete response rate in very-high-risk T1 disease, phase 2) show that immunotherapy-BCG combination strategies in this field are maturing rapidly.
Conclusion
The expanded analyses of the POTOMAC trial and the FDA approval based on them can be regarded as the beginning of a new era in which immunotherapy-BCG combinations enter clinical practice in the treatment of high-risk NMIBC. Long-term survival data and real-world experience will clarify which patient subgroups derive the greatest benefit from this combination. For the uro-oncology community, additional data from the CREST and ALBAN trials in the period ahead will also be decisive in shaping this treatment paradigm.
References
- FDA. FDA approves durvalumab in combination with BCG for high-risk NMIBC. 28 May 2026. - fda.gov
- Urology Times. AUA 2026: Expanded POTOMAC analyses support durvalumab plus BCG. - urologytimes.com
- OncLive. Durvalumab Plus BCG Reduces High-Risk NMIBC Recurrence or Death Risk by 32% in Phase 3 POTOMAC Trial. - onclive.com
- UroToday. AUA 2026 Plenary Headlines: Durvalumab (POTOMAC) and Pembrolizumab Combined with BCG in High-Risk NMIBC. - urotoday.com
- AJMC. FDA Approves Durvalumab Plus BCG as First Immunotherapy Combo Regimen for High-Risk NMIBC. - ajmc.com
- AstraZeneca. IMFINZI regimen reduced early disease recurrence among high-risk NMIBC patients (POTOMAC exploratory analyses). - astrazeneca.com
- The Lancet. Durvalumab in combination with BCG for BCG-naive, high-risk NMIBC: final analysis of POTOMAC. - sciencedirect.com
Important Note: This article is compiled from scientific publications for general information purposes only and does not constitute individual medical advice. Always consult your physician regarding treatment decisions.
Dr. Murat Binbay - Urology, Uro-Oncology and Robotic Surgery
