Abstract
In castration-resistant prostate cancer (CRPC) patients, observational studies have reported that statins may boost the antitumor activity of abiraterone (AA) and data suggest an improvement in efficacy; conclusions with vitamin D are less clear but an eventual benefit has been pointed. We conducted a post hoc analysis of individual patient data of CRPC patients treated with prednisone and/or AA with or without statins/vitamin D on randomized clinical trials. In the COU-AA-301 trial, use of AA with statin and vitamin D reduced the risk of death by 38% (p = 0.0007) while AA alone was associated with a decrease of 10% (p = 0.025), compared to prednisone alone. Meanwhile, in the COU-AA-302 trial, use of AA plus statin plus vitamin D was associated with a reduced risk of death of 26% (p = 0.0054). In this data analysis from two prospective randomized clinical trials, statin and vitamin D use was associated with superior overall survival in metastatic CRPC patients treated with AA and prednisone. To our knowledge, this is the first report suggesting the impact of statin plus vitamin D in this population. New strategies using big data may help to clarify these questions easily and in a most cost-effective approach.
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References
Graaf MR, Beiderbeck AB, Egberts ACG, Richel DJ, Guchelaar H-J. The risk of cancer in users of statins. J Clin Oncol. 2004;22:2388–94.
Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367:1792–802.
Ahn J, et al. Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst. 2008;100:796–804.
Di Lorenzo G, et al. Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol Focus. 2017. https://doi.org/10.1016/j.euf.2017.03.015.
Schweizer MT, Yu EY. Targeting intratumoral androgens: statins and beyond. Ther Adv Med Oncol. 2016;8:388–95.
Ramakrishnan S, et al. Association among plasma 1, 25(OH) 2D, ratio of 1,25(OH) 2D to 25(OH) D, and prostate cancer aggressiveness. Prostate. 2019;79:1117–24.
Manson JE, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380:33–44.
de Bono JS, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.
Ryan CJ, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.
Pujalte Martin M, et al. TAXOMET: a French prospective multicenter randomized controlled phase II study comparing docetaxel plus metformin versus docetaxel plus placebo in mCRPC. J Clin Oncol. 2019;37:5004.
Acknowledgements
This study, carried out under YODA Project #2016-1136, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and do not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The contents of this manuscript have been partially presented at ASCO 2019: de Velasco G, Lora D, Carretero-González A, Martín Soberón MC, Sepúlveda Sánchez JM, Lorente D, Castellano DE. Combination of statin/vitamin D and metastatic castration-resistant prostate cancer (mCRPC): A post hoc analysis of two randomized clinical trials. Journal of Clinical Oncology 2019; 37, no. 15_suppl (May 20, 2019) 6617-6617.
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The authors listed below have made substantial contributions to the intellectual content of the paper in the various sections described below: Conception and design: GdV, ACG, DLora, RM, DLorente, DC. Acquisition of data: GdV, DLora. Analysis and interpretation of data: GdV, ACG, DLora. Drafting of manuscript: ACG, GdV, RM, DLorente. Revision of the manuscript: GdV, DC, RM, ACG. Statistical analysis: DLora. Obtaining funding: GdV. Administrative, technical, or material support: ACG, GdV, DLora, RM, DLorente, DC. Supervision: DC, GdV.
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A. Carretero-González: none. D. Lora: none. R. Manneh: none. D. Lorente: none. D. Castellano: honoraria/consulting role/research funding: Roche, MSD, Exelixis, Pfizer, AstraZeneca, Janssen, Astellas, Ipsen. G. de Velasco: honoraria/consulting role/research funding: Pfizer, Novartis, Ipsen, Bristol-Myers Squibb, Bayer, Roche, Astellas, MSD.
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This study, carried out under YODA Project #2016-1136, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and do not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C.
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Carretero-González, A., Lora, D., Manneh, R. et al. Combination of statin/vitamin D and metastatic castration-resistant prostate cancer (CRPC): a post hoc analysis of two randomized clinical trials. Clin Transl Oncol 22, 2126–2129 (2020). https://doi.org/10.1007/s12094-020-02334-6
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DOI: https://doi.org/10.1007/s12094-020-02334-6