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.


Wilson, Brooke E ORCID: 0000-0001-6557-7298, Armstrong, Andrew J ORCID: 0000-0001-7012-1754, de Bono, Johann ORCID: 0000-0002-2034-595X, Sternberg, Cora N ORCID: 0000-0003-3938-2627, Ryan, Charles J, Scher, Howard I, Smith, Matthew R, Rathkopf, Dana, Logothetis, Christopher J, Chi, Kim N ORCID: 0000-0002-3782-7226 et al (show 9 more authors) (2022) 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 (Oxford, England : 1990), 170. pp. 296-304.

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Abstract

<h4>Background</h4>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.<h4>Objective</h4>To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR.<h4>Design, setting and participant</h4>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 χ<sup>2</sup> test.<h4>Results</h4>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).<h4>Conclusion</h4>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.

Item Type: Article
Uncontrolled Keywords: Humans, Metformin, Prednisone, Prostate-Specific Antigen, Antineoplastic Combined Chemotherapy Protocols, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Disease-Free Survival, Treatment Outcome, Castration, Male, Prostatic Neoplasms, Castration-Resistant, Abiraterone Acetate
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 30 Jan 2024 11:17
Last Modified: 30 Jan 2024 11:40
DOI: 10.1016/j.ejca.2022.03.042
Open Access URL: https://doi.org/10.1016/j.ejca.2022.03.042
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3178136
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