Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (34)
Neil E. Fleshner
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Rui M. Bernardino
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Jonathan Izawa
University of Western Ontario, London, ON, Canada
Darrel Drachenberg
Manitoba Prostate Cancer, University of Manitoba, Winnipeg, MB, Canada
Jeff W. Saranchuk
CancerCare Manitoba, Winnipeg, MB, Canada
Adrian Fairey
Northern Alberta Urology Clinic, Edmonton, AB, Canada
Simon Tanguay
McGill University Health Centre, Montréal, QC, Canada
Michael Leveridge
Queen's University, Kingston, ON, Canada
Fred Saad
Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal
Rodney H. Breau
University of Ottawa, Ottawa
Bobby Shayegan
Laurence Klotz
Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
Karen Hersey
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Sunakshi Chowdhary
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Karen Chadwick
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Heidi Wagner
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Tiiu Sildva
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Shabbir M.H. Alibhai
Naghmeh Rastegar
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Miran Kenk
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Rosette Veloso
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Jessica G. Cockburn
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Joan Sweet
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Clare O'Connell
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Linda Kapusta
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Aingeshaan Kubendran
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Tabassom Azizi
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Doron Berlin
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Robert J. Hamilton
Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Katherine Lajkosz
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Theodorus van der Kwast
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Ricardo A. Rendon
Department of Urology, Dalhousie University, Halifax, NS, Canada
Patrick O. Richard
Anthony M. Joshua
Immunology Division, Garvan Institute of Medical Research