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

• Published in: European journal of cancer (1990) 2022-07, Vol.170, p.296-304
• Main Authors: Wilson, Brooke E., Armstrong, Andrew J., de Bono, Johann, Sternberg, Cora N., Ryan, Charles J., Scher, Howard I., Smith, Matthew R., Rathkopf, Dana, Logothetis, Christopher J., Chi, Kim N., Jones, Robert J., Saad, Fred, De Porre, Peter, Tran, NamPhuong, Hu, Peter, Gillessen, Silke, Carles, Joan, Fizazi, Karim, Joshua, Anthony M.
• Format: Article
• Language: English
• Subjects: Abiraterone acetate; Abiraterone Acetate - therapeutic use; Acetic acid; Antidiabetics; Antigens; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Castration; Chi-square test; Clinical trials; Disease-Free Survival; Hazards; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Male; Metastases; Metastasis; Metastatic castration-resistant prostate cancer; Metformin; Metformin - therapeutic use; Prednisolone; Prednisone; Prednisone - therapeutic use; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - pathology; Secondary analysis; Statins; Statistical models; Treatment Outcome
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.03.042

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. To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR. 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. 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). 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. •We examined the effect of metformin and statins on outcomes in registrational abiraterone acetate plus prednisone/prednisolone trials.•Results were inconsistent across subgroups and trials with respect to prostate-specific antigen response rate and overall survival.•Pooled analyses suggests prolonged overall survival with metformin or statins.•These results need prospective evaluation in ongoing trials.