Metformin Active Surveillance Trial in Low-Risk Prostate Cancer

Author(s): Neil E. Fleshner, MD¹; Rui M. Bernardino, MD¹; Jonathan Izawa, MD²; Darrel Drachenberg, MD³; Jeff W. Saranchuk, MD⁴; Adrian Fairey, MD⁵; Simon Tanguay, MD⁶; Michael Leveridge, MD⁷; Fred Saad, MD⁸; Rodney H. Breau, MD⁹; Bobby Shayegan, MD¹⁰; Laurence Klotz, MD¹¹; Karen Hersey, RN¹; Sunakshi Chowdhary, MSc¹; Karen Chadwick, MSc¹; Heidi Wagner, MBA, PA¹; Tiiu Sildva, RN, MPH¹; Shabbir M.H. Alibhai, MD¹²; Naghmeh Rastegar, MSc¹; Miran Kenk, PhD¹; Rosette Veloso, IMD¹; Jessica G. Cockburn, PhD¹; Joan Sweet, MD¹³; Clare O’Connell, MBBCh¹; Linda Kapusta, MD¹³; Aingeshaan Kubendran, BScH¹; Tabassom Azizi, MD¹; Doron Berlin, BSc¹; Robert J. Hamilton, MD¹; Katherine Lajkosz, MSc¹⁴; Theodorus van der Kwast, MD¹³; Ricardo A. Rendon, MD¹⁵; Patrick O. Richard, MD¹⁶; Anthony M. Joshua, MD, PhD¹⁷;

Source: DOI: 10.1200/JCO-25-01070

Dr. Maen Hussein's Thoughts

Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.

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 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.

Author Affiliations

¹Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; ²University of Western Ontario, London, ON, Canada; ³Manitoba Prostate Cancer, University of Manitoba, Winnipeg, MB, Canada; ⁴CancerCare Manitoba, Winnipeg, MB, Canada; ⁵Northern Alberta Urology Clinic, Edmonton, AB, Canada; ⁶McGill University Health Center, Montreal, QC, Canada; ⁷Queen's University, Kingston, ON, Canada; ⁸Centre Hospitalier de l'Universit?? de Montr??al, University of Montreal, Montreal, QC, Canada; ⁹Ottawa Hospital, Ottawa, ON, Canada; ¹⁰St Josephs Healthcare, McMaster University, Hamilton, ON, Canada; ¹¹Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; ¹²Department of Medicine, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; ¹³Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; ¹⁴Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; ¹⁵Department of Urology, Dalhousie University, Halifax, NS, Canada; ¹⁶CIUSSS de l'Estrie???CHUS (Hopital Fleurimont), Sherbrooke, QC, Canada; ¹⁷St Vincent's Hospital Sydney, Sydney, NSW, Australia

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