Enzalutamide Plus Metformin Versus Enzalutamide Alone in Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 2 Trial (SAKK 08/14)

Background and objective: The aim of our study is to determine whether the addition of metformin to enzalutamide can improve the outcomes of men with metastatic castration-resistant prostate cancer (mCRPC).Methods: From 2016 to 2021, patients with mCRPC were randomized to receive enzalutamide plus metformin or enzalutamide alone, with body mass index (BMI) as a stratification factor.Primary end point was disease-control rate (DCR) at 15 mo.Secondary end points included event-free survival (EFS), time to prostate-specific antigen progression (TTPSAP) or radiologic progression (TTRP), and overall survival (OS).Post hoc analyses include tumor phosphatase and tensin homolog (PTEN)-protein expression.Key findings and limitations: Enzalutamide plus metformin (n = 84) did not increase DCR or secondary end points compared with enzalutamide alone (n = 82; DCR 52% vs 56%, p = 0.64).Post hoc analysis suggests that addition of metformin to enzalutamide may improve TTPSAP (p = 0.0074) in patients with PTEN-expressing tumor (n = 64),