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Metformin does not prevent progression of low-risk prostate cancer

Presented by
Dr Antony Joshua, Princes Margret Cancer Center, Canada
ASCO 2024
Patients with low-risk, localised prostate cancer who are suitable for active surveillance do not benefit from (daily) use of metformin. In patients with high BMI, metformin is potentially detrimental, results from the MAST study suggest.

Previously, it was suggested that metformin could serve as a useful adjuvant agent in cancer management, with the greatest benefits seen in colorectal and prostate cancer [1]. Biological, epidemiological, and clinical data support a rationale for the use of metformin in prostate cancer. However, much of the literature is focused on retrospective analyses, with metformin use being associated with type 2 diabetes.

The MAST trial (NCT01864096) is the first, prospective, and randomised study to explore the effect of daily use of metformin on the progression of low-risk, localised prostate cancer. Dr Antony Joshua (Princes Margret Cancer Center, Canada) presented the results [2].

In the study, 407 men (newly diagnosed with low-risk prostate cancer: Gleason score ‚ȧ6, ‚ȧ1/3 positive biopsy cores, <50% of any one core positive, clinical stage T1c-T2a, PSA ‚ȧ10 ng/ml) were 1:1 randomised to active surveillance plus metformin or active surveillance plus placebo. Patients diagnosed with type 1 or type 2 diabetes were excluded. Primary endpoints were time to pathological progression and time to definitive therapy. Biopsies were taken at baseline and at 18 and 36 months of follow-up.

Metformin did not delay pathological progression versus placebo (HR 1.08; 95% CI 0.78-1.50; P=0.64) but did increase therapeutic progression (HR 1.75; 95% CI 0.99-3.03; P= 0.05). Exploratory subgroup analysis showed significantly increased pathological progression in patients with BMI ‚Č•30 at study entry (n=105) treated with metformin versus placebo (HR 2.39; 93% CI 1.20-4.75; P=0.01). In addition, in patients with Gleason ‚Č•8 (n=11) a trend was observed for increased progression on metformin.

Based on these results, Dr Joshua concluded: ‚ÄúMetformin does not prevent progression of low-risk, localised prostate cancer suitable for active surveillance. In patients with a high BMI, metformin could even be detrimental. Therefore, further research is needed to understand the consequences of metformin on prostate cancer outcomes.‚ÄĚ

  1. Coyle C, et al. Ann Oncol. 2016;27:2184-2195.
  2. Joshua A, et al. A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: the MAST (Metformin Active Surveillance Trial) study. Abstract LBA5002, ASCO Annual Meeting 2024, 31 May-4 June, Chicago, IL, USA.

Medical writing support was provided by Marten Dooper, PhD.

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