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 Journal Article

   

Authors:	Wilson, B. E.; Armstrong, A. J.; de Bono, J.; Sternberg, C. N.; Ryan, C. J.; Scher, H. I.; Smith, M. R.; Rathkopf, D.; Logothetis, C. J.; Chi, K. N.; Jones, R. J.; Saad, F.; De Porre, P.; Tran, N.; Hu, P.; Gillessen, S.; Carles, J.; Fizazi, K.; Joshua, A. M.
Article Title:	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
Abstract:	Background: 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. © 2022 The Authors
Keywords:	adult; cancer survival; controlled study; treatment outcome; treatment response; disease-free survival; major clinical study; overall survival; prednisone; placebo; disease free survival; antineoplastic agent; prostate specific antigen; heart disease; antineoplastic combined chemotherapy protocols; drug effect; pathology; retrospective study; docetaxel; prostate-specific antigen; hypokalemia; prednisolone; abiraterone acetate; castration; hydroxymethylglutaryl coenzyme a reductase inhibitor; metformin; castration resistant prostate cancer; secondary analysis; post hoc analysis; randomized controlled trial (topic); hydroxymethylglutaryl-coa reductase inhibitors; clinical outcome; statins; metastatic castration-resistant prostate cancer; humans; human; male; article; prostatic neoplasms, castration-resistant; metastatic castration resistant prostate cancer
Journal Title:	European Journal of Cancer
Volume:	170
ISSN:	0959-8049
Publisher:	Elsevier Inc.
Date Published:	2022-07-01
Start Page:	296
End Page:	304
Language:	English
DOI:	10.1016/j.ejca.2022.03.042
PUBMED:	35568679
PROVIDER:	scopus
PMCID:	PMC9949683
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85130352313&doi=10.1016%2fj.ejca.2022.03.042&partnerID=40&md5=dd427ea3b0d9e25dec2c1f1563fb92c3
Notes:	Article -- Export Date: 1 August 2022 -- Source: Scopus

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