Metformin does not prevent prostate cancer progression on active surveillance

Metformin did not slow the rate of progression among men with low-risk, localized prostate cancer who are suitable for active surveillance, according to data from the Metformin Active Surveillance Trial (MAST; NCT01864096), which was presented at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.¹

“The key takeaway point is that metformin does not prevent progression of low-risk localized prostate cancer suitable for active surveillance," says Anthony M. Joshua, BSc(Med), MBBS, PhD, FRACP.

In fact, data from the study indicated that metformin may negatively affect men with a high body mass index (BMI) and those with grade group 4+ (Gleason 8+) at progression.

Overall, the MAST trial sought to explore the use of metformin, an oral hypoglycemic agent known for its efficacy in diabetes, in a group of men newly diagnosed with generally very low to low-risk prostate cancer who are suitable for active surveillance.

Data showed no statistically significant difference in progression-free survival among those who received metformin vs those who received placebo (P = .63).

The results showed the inferiority of metformin compared with placebo regarding therapeutic progression (unadjusted HR, 1.75, CI, 0.99-3.08; P = .05), pathological progression (unadjusted HR, 1.07; CI, 0.76-1.52; P = .69), and therapeutic and pathologic progression together (unadjusted HR, 1.08; CI, 0.78-1.50; P = .64).

The 2 arms were also generally equivalent regarding the percentage of patients with more than one-third the total amount of cores involved, the max percentage of patients with at least 50% of any 1 core involved, and patients with Gleason 7 or higher. However, the investigators noted a trend toward imbalance in those who progressed to Gleason greater than 8 among those receiving metformin vs placebo (12.9% vs 4.5%; P = .82).

Similarly, metformin was shown to have detriment regarding pathologic progression compared with placebo in patients with a BMI of 30 or higher (unadjusted HR, 2.39; P = .01). There was no significant difference seen between the 2 groups for those with a BMI below 30.

Metformin was also shown to have no meaningful effect on prostate-specific antigen kinetics.

Regarding safety, 29% of patients in the metformin arm experienced grade 1/2 GI symptoms vs 3% of patients in the placebo arm. Additionally, 18% of patients receiving metformin experienced grade 1/2 diarrhea vs 8% of patients receiving placebo.

Patients in the metformin arm also experienced an average decrease of 1.8 kg in weight by 12 months in the study, vs an average increase of 0.6 kg in the placebo arm. At 24 months, the average weight change was a 1.4 kg decrease in the metformin arm and a 0.7 kg increase in the placebo arm.

Overall, the MAST study enrolled patients with very low to low-risk prostate cancer per National Comprehensive Cancer Center criteria. Patients were enrolled across 12 clinical trial sites in Canada from October 2013 to December 2023. Those included in the trial were randomly assigned 1:1 to either active surveillance plus placebo (n = 203) or to active surveillance plus metformin (n = 204).

The primary end points for the study were the time to definitive therapy, defined as prostatectomy, radiation, hormonal therapy, or focal therapy, as well as the time to pathological progression, defined as either greater than 1/3 the total amount of cores involved, at least 50% of any 1 core involved, or Gleason pattern 4 or higher.

Anthony M. Joshua, BSc(Med), MBBS, PhD, FRACP, who presented the data at ASCO, concluded in the presentation, “The key takeaway point is that metformin does not prevent progression of low-risk localized prostate cancer suitable for active surveillance. Exploratory subgroup analyses indicate potential detriment to patients with a high BMI at study entry and patients who progress with a high Gleason score at progression, and further research is needed.”

REFERENCE

1. Fleshner NE, Bernardino RM, Lajkosz K, 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. Presented at: 2024 American Society for Clinical Oncology Annual Meeting. May 31-June 4, Chicago, Illinois. Abstract LBA5002. https://meetings.asco.org/abstracts-presentations/239173