Type of publication:
Conference abstract
Author(s):
Gillessen S.; Murphy L.R.; James N.D.; Sachdeva A.; Attard G.; Jones R.J.; Adler A.; El-Taji O.; Varughese M.; Gale J.; Brown S.J.; Srihari N.N.; Millman R.; Matheson D.; Amos C.L.; Murphy C.; McAlpine C.; Parmar M.K.; Brown L.C.; Clarke N.
Citation:
Annals of Oncology. Conference: ESMO Congress 2024. Barcelona Spain. 35(Supplement 2) (pp S1258-S1259), 2024. Date of Publication: September 2024.
Abstract:
Background: Metformin is a widely used, well tolerated anti-diabetic agent. Several studies suggest metformin has anti-cancer activity in different malignancies, including prostate cancer. We hypothesised that metformin also reduces the development of ADT-induced metabolic adverse effects, possibly improving OS via these mechanisms. Method(s): Non-diabetic pts with mHSPC were randomly allocated 1:1 to standard of care (SOC) or SOC+metformin within STAMPEDE. SOC included ADT +/- radiotherapy +/- docetaxel +/- androgen receptor pathway inhibitor (ARPI). The primary outcome was OS. Target hazard ratio (HR) 0.8 (92% power, 2.5% 1-sided significance). 7 subgroup analyses were pre-specified but not pre-powered. Result(s): 1874 pts with mHSPC were randomised Sep2016-Mar2023. Arms were well balanced: median age 69 years, IQR 63-73; median PSA 84ng/ml, IQR 24-352; de novo 1758 (94%) vs relapsed 116 (6%). Planned SOC included 82% Docetaxel and 3% ARPI. After a median follow-up of 60 months, the HR for OS between arms was 0.91 (p=0.148; 95% CI 0.80-1.03). The median (95%CI) OS was 63 (58-69) and 69 (63-73) months in the SOC and SOC+metformin arms respectively. In patients with high versus low volume disease (CHAARTED def), HR was 0.79 (p=0.006; 0.66-0.93) and 1.0 (p=0.992; 0.79-1.26) respectively. The interaction p-value = 0.086. For progression-free survival: Overall HR was 0.92 (p=0.164; 0.81-1.04) with HRs of 0.76 (p=0.001; 0.64-0.89) and 1.10 (p=0.401; 0.88-1.37) in the high and low volume subgroups respectively, interaction p-value = 0.006. Metabolic parameters that improved significantly with metformin included reduced weight gain, fasting glucose, HbA1c and total and LDL cholesterol. Fewer patients developed a metabolic syndrome. Adverse events (AE) >=grade 3 were reported in 52% and 57% in the SOC and SOC+metformin arms, respectively; Gastrointestinal AEs increased with metformin. Conclusion(s): Metformin does not improve survival in unselected metastati
