In the final analysis of the phase III POTOMAC trial reported in The Lancet, De Santis et al found that the addition of durvalumab to bacillus Calmette-Guérin (BCG) induction and maintenance improved disease-free survival in patients with high-risk non–muscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT).
Study Details
In the open-label trial, 1,018 patients from sites in 12 countries were randomly assigned 1:1:1 between June 2018 and October 2020 to receive either:
- Durvalumab at 1,500 mg every 4 weeks for 13 cycles plus BCG induction (weekly for 6 weeks) and maintenance (three doses at weekly intervals at 3, 6, 12, 18, and 24 months; n = 339)
- Durvalumab plus BCG induction (n = 339)
- BCG induction and maintenance (comparison group, n = 340).
Durvalumab was given for up to 1 year; BCG induction and maintenance were given for up to 2 years. The primary endpoint was investigator-assessed disease-free survival in the durvalumab plus BCG induction and maintenance group vs the comparison group in the intention-to-treat population.
Key Findings
At a median follow-up of 60.7 months (interquartile range = 51.5–66.5 months), disease-free survival events had occurred in 67 patients (20%) in the durvalumab plus BCG induction and maintenance group vs 98 patients (29%) in the comparison group (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.50–0.93, P = .015). Proportions of patients alive without high-risk recurrence at 24 months were 86.5% vs 81.6%.
In the durvalumab plus BCG induction group, disease-free survival events were observed in 105 patients (31%), with no significant difference being observed vs the control group (HR = 1.14, 95% CI = 0.86–1.50, P = .35).
Grade 3 or 4 treatment-related adverse events occurred in 21% of the durvalumab plus BCG induction and maintenance group, 15% of the durvalumab plus BCG induction group, and 4% of the comparison group. The most common treatment-related adverse event of any grade in all groups was dysuria (33%, 18%, and 32%, respectively). Treatment-related serious adverse events occurred in 13%, 11%, and 4% of patients; no treatment-related deaths were reported.
The investigators concluded: “Among patients with BCG-naive, high-risk NMIBC, 1 year of durvalumab combined with BCG induction and maintenance therapy showed a statistically significant and clinically meaningful improvement in disease-free survival vs BCG induction and maintenance alone. The combination had a manageable safety profile, consistent with that of the individual therapies. These results support 1 year of durvalumab in combination with BCG induction and maintenance therapy as a potential new treatment for this patient population.”
Neal D. Shore, MD, of START Carolinas/Carolina Urologic Research Center, Myrtle Beach, South Carolina, is the corresponding author for The Lancet article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of all study authors, visit thelancet.com.
