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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.

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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.
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