Adding metformin to androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): Quality of life (QoL) results from STAMPEDE.

135 Background: ADT, the standard treatment for mHSPC, induces metabolic side effects that impact QoL. In the STAMPEDE trial, metformin improved metabolic parameters, and had a signal for oncological benefit in high-volume disease. Its potential to enhance QoL remains clinically relevant. Methods: Men with mHSPC were randomly allocated 1:1 to standard of care (SOC: ADT ± docetaxel ± radiotherapy) ± metformin. Diabetic patients were ineligible. Patients completed EORTC QLQ-C30 and PR25 questionnaires at baseline and regular intervals for up to two years. The primary analysis assessed longitudinal global QoL using linear mixed models with a time-by-treatment interaction, adjusting for baseline. Cross-sectional analyses were conducted at predefined timepoints. A between-arm difference ≥ 4 points on the transformed 0–100 scale defined clinical relevance for our primary outcome. Functional domains and symptom scores were also compared. Results: A total of 996 men completed baseline and at least one further QoL assessment up to 24 months (SOC: 443; SOC + metformin: 553). Clinical characteristics were well balanced across groups. Global QoL over two years did not differ between arms (mean difference = +1.1 [95% CI –0.7 to 3.0]; p = 0.24, favouring metformin). Functional domains were similar: small improvements in emotional (+2.2; p = 0.008) and cognitive (+2.2; p = 0.007) function were evident but this did not reach clinical significance. Physical and social functioning were similar, as were fatigue, and pain. Diarrhoea was more frequent with metformin (+5.8; p < 0.001). Treatment-related symptoms (PR25 composite) favoured metformin (–2.4; p < 0.001) but were below the threshold for clinical significance. Findings in men with high-volume disease were consistent with the primary analysis, showing non-significant improvements in global QoL with metformin. Conclusions: Metformin is safe, inexpensive, and well tolerated in men with mHSPC receiving standard therapy. Overall QoL was maintained, with no deterioration across functional domains and only a modest, manageable increase in diarrhoea. Small improvements in emotional, cognitive, and treatment-related symptoms were observed, supporting metformin’s favourable tolerability profile alongside its known metabolic benefits. Clinical trial information: NCT00268476 .