TY - JOUR
T1 - Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide
T2 - A meta-analysis of AFFIRM, PREVAIL and PROSPER
AU - Joshua, Anthony M.
AU - Armstrong, Andrew
AU - Crumbaker, Megan
AU - Scher, Howard I.
AU - de Bono, Johann
AU - Tombal, Bertrand
AU - Hussain, Maha
AU - Sternberg, Cora N.
AU - Gillessen, Silke
AU - Carles, Joan
AU - Fizazi, Karim
AU - Lin, Ping
AU - Duggan, William
AU - Sugg, Jennifer
AU - Russell, David
AU - Beer, Tomasz M.
N1 - Funding Information:
This study was sponsored by Pfizer Inc. (New York, NY, USA) and Astellas Pharma, Inc . (Northbrook, IL, USA), the co-developers of enzalutamide. Medical writing and editorial support funded by the sponsors were provided by Stephanie Vadasz, PhD, and Dena McWain of Ashfield MedComms (an Ashfield Health company), Lauren Rainer, BSc, and Julie B. Stimmel, PhD, of Onyx (a Prime Global agency).
Funding Information:
TMB in the past year reports: institutional research funding from Alliance Foundation Trials, Astellas Pharma, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc., Freenome, Grail Inc, Harpoon Therapeutics, Janssen Research & Development, Medivation, Inc., Sotio, Theraclone Sciences/OncoResponse, and Zenith Epigenetics; has consulted for: Arvinas, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Constellation, Grail Inc, Janssen, Myovant Sciences, Pfizer, and Sanofi, and holds stock in Arvinas Inc, and Salarius Pharmaceuticals.
Funding Information:
AA is a paid consultant for and/or receives institutional funding from Astellas, Pfizer, Janssen, Bayer, Dendreon, Genentech/Roche, Bristol Myers Squibb, Merck, and AstraZeneca. AA provides research support to Duke University from Constellation, Beigene, Amgen, Celgene, and Forma.
Funding Information:
AMJ declares consultant/advisory board member for Neokulin, Janssen Oncology, Ipsen, AstraZeneca, Sanfoi, Noxopharm, IQvia, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, Eisai. AMJ has received research funding from: Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genetech, Bayer, Macrogenics, Lilly, Pfizer, AstraZeneca, and Corvus Pharmaceuticals.
Funding Information:
HIS declares consultant/advisory board member for Ambry Genetics Corporation, Amgen, Bayer, ESSA Pharma, Janssen Biotech, Janssen Research & Development, OncLive Insights, Menarini Silicon Biosystems, Physicians Education Resource, Pfizer, Sanofi Aventis, Sun Pharmaceuticals Industries, Inc. and WCG Oncology; Board of Directors’ Member of Asterias Biotherapeutics; Intellectual Property Rights BioNTech, Elucida Oncology, MaBVAX, Y-mAbs Therapeutics, Inc and institutional research funding from Epic Sciences, Illumina, Janssen Diagnostics, Menarini Silicon Biosystems, and ThermoFisher.
Publisher Copyright:
© 2022 The Pfizer, The Author(s)
PY - 2022/7
Y1 - 2022/7
N2 - Background: Statins and metformin are commonly prescribed for patients, including those with prostate cancer. Preclinical and epidemiologic studies of each agent have suggested anti-cancer properties. Methods: Patient data from three randomised, double-blind, placebo-controlled, phase III studies evaluating enzalutamide (AFFIRM, PREVAIL and PROSPER) in patients with castration-resistant prostate cancer were included in this analysis. This post hoc, retrospective study examined the association of statin and metformin on radiographic progression-free survival (rPFS), metastasis-free survival (MFS), toxicity and overall survival (OS). After adjusting for available clinical prognostic variables, multivariate analyses were performed on pooled data from AFFIRM and PREVAIL, all three trials pooled, and each trial individually, to assess differential efficacy in these end-points associated with the baseline use of these medications. Results: In the multivariate analysis of the individual trials, OS and rPFS/MFS were not significantly influenced by statin or metformin use in AFFIRM or PROSPER. However, in PREVAIL, OS was significantly influenced by statin (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.59–0.89) and rPFS was significantly influenced by metformin (HR, 0.48; 95% CI 0.34–0.70). In pooled analyses, improved OS was significantly associated with statin use but not metformin use for AFFIRM+PREVAIL trials (HR 0.83; 95% CI 0.72–0.96) and AFFIRM+PREVAIL+PROSPER (HR 0.75; 95% CI 0.66–0.85). Conclusions: The association between statin or metformin use and rPFS, MFS and OS was inconsistent across three trials. Analyses of all three trials pooled and AFFIRM+PREVAIL pooled revealed that statin but not metformin use was significantly associated with a reduced risk of death in enzalutamide-treated patients. Additional prospective, controlled studies are warranted. Clinical trial registration: AFFIRM (NCT00974311), PREVAIL (NCT01212991) and PROSPER (NCT02003924).
AB - Background: Statins and metformin are commonly prescribed for patients, including those with prostate cancer. Preclinical and epidemiologic studies of each agent have suggested anti-cancer properties. Methods: Patient data from three randomised, double-blind, placebo-controlled, phase III studies evaluating enzalutamide (AFFIRM, PREVAIL and PROSPER) in patients with castration-resistant prostate cancer were included in this analysis. This post hoc, retrospective study examined the association of statin and metformin on radiographic progression-free survival (rPFS), metastasis-free survival (MFS), toxicity and overall survival (OS). After adjusting for available clinical prognostic variables, multivariate analyses were performed on pooled data from AFFIRM and PREVAIL, all three trials pooled, and each trial individually, to assess differential efficacy in these end-points associated with the baseline use of these medications. Results: In the multivariate analysis of the individual trials, OS and rPFS/MFS were not significantly influenced by statin or metformin use in AFFIRM or PROSPER. However, in PREVAIL, OS was significantly influenced by statin (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.59–0.89) and rPFS was significantly influenced by metformin (HR, 0.48; 95% CI 0.34–0.70). In pooled analyses, improved OS was significantly associated with statin use but not metformin use for AFFIRM+PREVAIL trials (HR 0.83; 95% CI 0.72–0.96) and AFFIRM+PREVAIL+PROSPER (HR 0.75; 95% CI 0.66–0.85). Conclusions: The association between statin or metformin use and rPFS, MFS and OS was inconsistent across three trials. Analyses of all three trials pooled and AFFIRM+PREVAIL pooled revealed that statin but not metformin use was significantly associated with a reduced risk of death in enzalutamide-treated patients. Additional prospective, controlled studies are warranted. Clinical trial registration: AFFIRM (NCT00974311), PREVAIL (NCT01212991) and PROSPER (NCT02003924).
KW - Castration-resistant prostate cancer
KW - Enzalutamide
KW - Metformin
KW - Overall survival
KW - Radiographic progression-free survival
KW - Statin
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U2 - 10.1016/j.ejca.2022.04.005
DO - 10.1016/j.ejca.2022.04.005
M3 - Article
C2 - 35643841
AN - SCOPUS:85130310825
VL - 170
SP - 285
EP - 295
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -