Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
Neil Fleshner, Rui Bernardino, Jonathan I. Izawa, Darrel Drachenberg, Jeff Saranchuk, Adrian Fairey, Simon Tanguay, Michael Leveridge, Fred Saad, Rodney H. Breau, Bobby Shayegan, Laurence H. Klotz, Karen Hersey, Sunakshi Chowdhary, Karen Chadwick, Heidi Wagner, Tiiu Sildva, Shabbir M.H. Alibhai, Naghmeh Rastegar, Miran Kenk, Rosette Veloso, Jessica Cockburn, Joan Sweet, Clare O’Connell, Linda Kapusta, Aingeshaan Kubendran, Tabassom Azizi, Doron Berlin, Robert J. Hamilton, Katherine Lajkosz, Theodorus van der Kwast, Ricardo Rendon, Patrick O. Richard, Anthony M. Joshua
Abstract
PURPOSE Active surveillance (AS) is a standard management strategy for low-risk prostate cancer (PCa), but a significant proportion of patients ultimately experience disease progression. Metformin, a commonly prescribed antidiabetic agent, has demonstrated antitumor activity in preclinical studies and observational data, prompting investigation into its potential to delay PCa progression. PATIENTS AND METHODS The Metformin Active Surveillance Trial (MAST) was a multicenter, randomized, double-blind, placebo-controlled phase III trial evaluating the efficacy of metformin in men with low-risk, localized PCa managed with AS. Eligible participants were randomly assigned 1:1 to receive either metformin (850 mg twice daily) or placebo and were followed for up to 36 months. The primary end point was time to progression, defined as therapeutic and/or pathologic progression. Progression-free survival (PFS) was assessed using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS A total of 408 patients were randomly assigned (205 metformin, 203 placebo). After a median follow-up of 36 months, 144 participants experienced progression (70 metformin, 74 placebo), with no significant difference in PFS (hazard ratio [HR], 1.09 [95% CI, 0.79 to 1.52]; P = .59). Negative biopsy rates at 36 months were 41.0% (metformin) versus 31.1% (placebo; P = .181). In prespecified subgroup analysis, metformin was associated with increased pathologic progression among obese patients (BMI ≥ 30; HR, 2.36 [95% CI, 1.21 to 4.59]; P = .0092). CONCLUSION Metformin did not reduce progression in men with low-risk PCa on AS. The observed adverse effect in obese patients merits further investigation.