Enzalutamide Plus Metformin Versus Enzalutamide Alone in Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 2 Trial (SAKK 08/14)
Abstract
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), but not in patients with PTEN-negative tumor (n = 65, p > 0.6). Patients who were overweight/obese at baseline (BMI ≥25 kg/m2) had better DCR, OS, EFS, TTPSAP, and TTRP than patients with BMI <25 kg/m2, independent of treatment arm (p < 0.009).
CONCLUSIONS AND CLINICAL IMPLICATIONS: The addition of metformin to enzalutamide did not improve the study end points in the whole study cohort. PTEN status as a potential predictive biomarker and the obesity…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 84 participants or records.
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