In a Canadian phase III trial (MAST) reported in the Journal of Clinical Oncology, Fleshner et al found that metformin did not improve progression-free survival vs placebo in men with low-risk prostate cancer undergoing active surveillance.
Study Details
In the multicenter double-blind trial, 408 patients undergoing active surveillance were randomly assigned between November 2013 and November 2023 to receive metformin at 850 mg twice daily (n = 205) or placebo (n = 203) for up to 36 months. The primary endpoint was progression-free survival.
Key Findings
After a median follow-up of 36 months, progression occurred in 70 patients in the metformin group and 74 in the placebo group, with no significant difference in progression-free survival being observed (hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 0.79–1.52, P = .59). Progression-free survival rates at 12, 24, and 36 months were 94% vs 96%, 62% vs 69%, and 58% vs 60%.
At 36 months, negative biopsy rates were 41.0% in the metformin group vs 31.1% in the placebo group (P = .181).
In subgroup analysis among obese patients, use of metformin was associated with increased risk of progression (HR = 2.36, 95% CI = 1.21–4.59, P = .0092).
Gastrointestinal adverse events of any grade were more common in the metformin group, including diarrhea (19% vs 8%) and nausea, dyspepsia, and abdominal pain (9% vs 1% each).
The investigators concluded: “Metformin did not reduce progression in men with low-risk [prostate cancer on active surveillance]. The observed adverse effect in obese patients merits further investigation.”
Neil E. Fleshner, MD, of the Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Canadian Cancer Research Institute, the Prostate Cancer Foundation, and the Princess Margaret Foundation—Hold’em for Life Challenge/Love Chair in Cancer. For full disclosures of all study authors, visit ascopubs.org.
