Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Jul:170:296-304.
doi: 10.1016/j.ejca.2022.03.042. Epub 2022 May 11.

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

Brooke E Wilson  1 , Andrew J Armstrong  2 , Johann de Bono  3 , Cora N Sternberg  4 , Charles J Ryan  5 , Howard I Scher  6 , Matthew R Smith  7 , Dana Rathkopf  8 , Christopher J Logothetis  9 , Kim N Chi  10 , Robert J Jones  11 , Fred Saad  12 , Peter De Porre  13 , NamPhuong Tran  14 , Peter Hu  15 , Silke Gillessen  16 , Joan Carles  17 , Karim Fizazi  18 , Anthony M Joshua  19
Affiliations
Randomized Controlled Trial

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

Brooke E Wilson et al. Eur J Cancer. 2022 Jul.

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.

Keywords: Abiraterone acetate; Metastatic castration-resistant prostate cancer; Metformin; Statins.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Figures

Fig. 1.
Fig. 1.
Survival in patients enrolled in COU-AA-301, stratified by AAP/placebo and metformin use. AAP, acetate plus prednisone/prednisolone.
Fig. 2.
Fig. 2.
Survival in patients enrolled in COU-AA-302, stratified by AAP/placebo and metformin use. AAP, acetate plus prednisone/prednisolone.
Fig. 3.
Fig. 3.
Survival in patients enrolled in COU-AA-301, stratified by AAP/placebo and statin use. AAP, acetate plus prednisone/prednisolone.
Fig. 4.
Fig. 4.
Survival in patients enrolled in COU-AA-302, stratified by AAP/placebo and statin use. AAP, acetate plus prednisone/prednisolone.
See this image and copyright information in PMC

Comment in

References

    1. Ryan CJ, Smith MR, De Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368(2):138–48. - PMC - PubMed
    1. De Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364(21):1995–2005. - PMC - PubMed
    1. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330(7503):1304–5. - PMC - PubMed
    1. Ruiter R, Visser LE, van Herk-Sukel MP, et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population-based follow-up study. Diabetes Care 2012;35(1):119–24. - PMC - PubMed
    1. Murtola TJ, Tammela TL, Lahtela J, Auvinen A. Antidiabetic medication and prostate cancer risk: a population-based case-control study. Am J Epidemiol 2008;168(8):925–31. - PubMed

Publication types

MeSH terms