Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302
AuthorsWilson, B. E.
Armstrong, A. J.
de Bono, J.
Sternberg, C. N.
Ryan, C. J.
Scher, H. I.
Smith, M. R.
Logothetis, C. J.
Chi, K. N.
Jones, R. J.
De Porre, P.
Joshua, A. M.
AffiliationPrincess Margaret Cancer Centre, Toronto, Canada; Faculty of Medicine, University of New South Wales, Kensington, Australia; Kinghorn Cancer Centre, St Vincents Hospital, Darlinghurst, Sydney, Australia
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AbstractBackground: The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear. Objective: To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR. Design, setting and participant: COU-AA-301 and COU-AA-302 patients were stratified by metformin and statin use. Cox proportional hazards models were used to estimate hazards ratio (HR) stratified by concomitant medications, and a random effects model was used to pool HR. We compared PSA-RR using Chi χ2 test. Results: In COU-AA-301-AAP, metformin was associated with improved PSA-RR (41.1% versus 28.6%) but not prolonged OS. In COU-AA-301-placebo-P, there was no association between metformin and prolonged OS or PSA-RR. In COU-AA-302-AAP, metformin was associated with prolonged OS (adjHR 0.69, 95% CI 0.48-0.98) and improved PSA-RR (72.7% versus 60.0%). In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66, 95% CI 0.47-0.93). In pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77, 95% CI 0.62-0.95).In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76, 95% CI 0.62-0.93), while there was no difference in COU-AA-301-P. There was no association with statins and OS in either COU-AA-302 groups. When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78, 95% CI 0.68-0.88). Conclusion: Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP.
CitationWilson BE, Armstrong AJ, de Bono J, Sternberg CN, Ryan CJ, Scher HI, et al. Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302. European Journal of Cancer. Elsevier BV; 2022.`
JournalEuropean Journal of Cancer
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