In a phase III trial (part of the STAMPEDE platform) reported in The Lancet Oncology, Gillessen et al investigated the survival outcomes of adding metformin to standard of care (SOC) in nondiabetic patients with metastatic hormone-sensitive prostate cancer starting androgen-deprivation therapy (ADT).
Study Details
In the open-label trial, 1,874 patients from sites in the United Kingdom and Switzerland were randomly assigned between September 2016 and March 2023 to receive SOC (n = 938) or metformin at 850 mg twice daily plus SOC (n = 936). Standard of care consisted of ADT with or without radiotherapy and with or without docetaxel or an androgen receptor pathway inhibitor (ARPI; docetaxel vs abiraterone, enzalutamide, or apalutamide). The primary endpoint was overall survival.
Key Findings
Median time to most recent patient follow-up was 60 months (interquartile range [IQR] = 49–72 months). Median overall survival was 67.4 months (IQR = 32.5 months to not reached) in the metformin-SOC group vs 61.8 months (IQR = 29.7 months to not reached) in the SOC group (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.80–1.03, P = .15).
Grade ≥ 3 adverse events occurred in 57% of the metformin-SOC group vs 52% of the SOC group, with grade ≥ 3 gastrointestinal adverse events in 9% vs 7%; no differences in grade ≥ 3 events in other body systems were observed.
Weight gain was significantly lower in the metformin-SOC group at 24, 48, and 104 weeks (all P < .0001). Among 583 patients with body weight data available at baseline and at 104 weeks, those in the metformin-SOC group gained a mean of 2.00 kg (95% CI = 1.31–2.69 kg) vs 4.40 kg (95% CI = 3.57–5.24 kg) in the SOC group (mean difference = –2.48 kg, 95% CI = –3.55 to –1.41 kg).
The investigators concluded: “We did not find significant evidence of an overall survival benefit of adding metformin to SOC in the overall population of patients with metastatic hormone-sensitive prostate cancer. The side-effect profile of metformin was as expected and consisted mainly of diarrhea. Adverse metabolic side effects of ADT were significantly reduced in the metformin group compared with the standard of care group.”
Silke Gillessen, MD, of the Institute of Oncology of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Cancer Research UK, Prostate Cancer UK, and UK Research and Innovation Medical Research Council. For full disclosures of all study authors, visit The Lancet Oncology.
