Metformin and statins improve overall survival in men with castration-resistant metastatic prostate cancer: Study
Canada: The use of metformin and statins results in prolonged overall survival and an improved response rate of prostate-specific antigen (PSA), particularly in combination with abiraterone acetate plus prednisone/prednisolone (AAP), results from a post hoc subanalysis indicates. The study appears in the European Journal of Cancer.
Brooke E.Wilson, Princess Margaret Cancer Centre, Toronto, Canada, and colleagues conducted the study with the objective to determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone influence OS and prostate-specific antigen response rate (PSA-RR) in patients with metastatic castration-resistant prostate cancer in the COU-AA-301 and COU-AA-302 trials.
COU-AA-301 and COU-AA-302 patients were stratified by the use of metformin and statin. Hazards ratio (HR) stratified by concomitant medications were estimated using Cox proportional hazards models. The random-effects model was used to pool HR.
Salient findings of the study include:
- 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) and improved PSA-RR (72.7% versus 60.0%).
- In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66).
- In the pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77).
- In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76), while there was no difference in COU-AA-301-P.
- There was no association between statins and OS in either COU-AA-302 group.
- When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78).
"The results although methodologically limited add to the growing body of evidence that metformin may prolong OS and increase PSA-RR among patients with mCRPC treated with AAP," wrote the authors.
"While our findings regarding the effects of statins on OS differed between chemotherapy-treated and chemotherapy-naïve patients, they highlight the need for further prospective and controlled clinical trials regarding the adjunctive role that these medications may play for men with mCRPC."
Reference:
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. 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. Eur J Cancer. 2022 May 11:S0959-8049(22)00205-2. doi: 10.1016/j.ejca.2022.03.042. Epub ahead of print. PMID: 35568679.
