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.
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Embargo End Date
ICR Authors
Authors
Wilson, BE
Armstrong, AJ
de Bono, J
Sternberg, CN
Ryan, CJ
Scher, HI
Smith, MR
Rathkopf, D
Logothetis, CJ
Chi, KN
Jones, RJ
Saad, F
De Porre, P
Tran, N
Hu, P
Gillessen, S
Carles, J
Fizazi, K
Joshua, AM
Armstrong, AJ
de Bono, J
Sternberg, CN
Ryan, CJ
Scher, HI
Smith, MR
Rathkopf, D
Logothetis, CJ
Chi, KN
Jones, RJ
Saad, F
De Porre, P
Tran, N
Hu, P
Gillessen, S
Carles, J
Fizazi, K
Joshua, AM
Document Type
Journal Article
Date
2022-07-01
Date Accepted
2022-03-16
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.
Citation
European Journal of Cancer, 2022, 170 pp. 296 - 304
Source Title
European Journal of Cancer
Publisher
ELSEVIER SCI LTD
ISSN
0959-8049
eISSN
1879-0852
1879-0852
1879-0852
Collections
Research Team
PrCa Targeted Therapy