Abiraterone Acetate: A Review of Its Use in Patients with Metastatic Castration-Resistant Prostate Cancer
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Abiraterone acetate (Zytiga®) is an orally administered, selective inhibitor of the 17α-hydroxylase and C17,20-lyase enzymatic activities of cytochrome P450 (CYP) 17. CYP17 is required for androgen biosynthesis, with androgen receptor signalling crucial in the progression from primary to metastatic prostate cancer. Abiraterone acetate is approved in the European Union and the US, in combination with prednisone or prednisolone, for the treatment of men with metastatic castration-resistant prostate cancer (CRPC). When administered in combination with prednisone in a placebo-controlled, multinational phase III study, abiraterone acetate significantly prolonged overall survival and radiographic progression-free survival (rPFS) in men with metastatic CRPC who had previously received docetaxel. In men with metastatic CRPC who had not previously received chemotherapy participating in a placebo-controlled, multinational phase III study, there was a strong trend towards an overall survival benefit, a significant prolongation in rPFS and significant delays in clinical decline, the need for chemotherapy and the onset of pain observed. Given the nature of the therapy, the overall tolerability profile of abiraterone acetate, in combination with prednisone, was acceptable in men with metastatic CRPC. Abiraterone acetate is associated with hypokalaemia, hypertension, and fluid retention or oedema, secondary to its mechanism of action, and with cardiac adverse events and hepatotoxicity; however, in the phase III studies the incidences of the most frequently reported grade 3 or 4 adverse events of special interest were relatively low. Although the final overall survival data in men with metastatic CRPC who have not previously received chemotherapy are awaited, current evidence indicates that abiraterone acetate is a useful option for the treatment of metastatic CRPC.
KeywordsDocetaxel Androgen Receptor DHEA Androgen Deprivation Therapy National Comprehensive Cancer Network
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.
- 5.National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: prostate cancer (Version 4.2013). 2013. http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf (Accessed 11 Nov 2013).
- 12.European Medicines Agency. ZYTIGA 250 mg tablets: summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002321/WC500112858.pdf (Accessed 11 Nov 2013).
- 13.Janssen Biotech Inc. ZYTIGA® (abiraterone acetate) tablets: prescribing information; 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202379s007lbl.pdf (Accessed 11 Nov 2013).
- 19.Attard G, Reid AH, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven [Erratum appears in J Clin Oncol. 2012;30(15):1896]. J Clin Oncol. 2008;26(28):4563–71.PubMedCrossRefGoogle Scholar
- 31.van Soest RJ, van Royen ME, de Morrée ES, et al. Effects on androgen receptor nuclear import by docetaxel, cabazitaxel, abiraterone, and enzalutamide: potential mechanism for cross-resistance in castration-resistant prostate cancer (CRPC) [abstract no. 5064]. J Clin Oncol. 2013;31(15 Suppl 1).Google Scholar
- 37.Logothetis CJ, Basch E, Molina A, et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012;13(12):1210–7.PubMedCrossRefGoogle Scholar
- 39.Harland S, Staffurth J, Molina A, et al. Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy. Eur J Cancer 2013;49(17):3648–57.Google Scholar
- 40.Saad F, Shore ND, Van Poppel H, et al. Abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy: interim analysis of the COU-AA-302 phase 3 trial [abstract no. 713]. J Urol. 2013;189(4 Suppl):e293.Google Scholar
- 41.Shore N, Ryan CJ, Mulders P, et al. The impact of abiraterone acetate therapy on patient-reported pain and functional status in chemotherapy-naïve patients with progressive, metastatic castration-resistant prostate cancer: results from an updated analysis [abstract no. 784]. J Urol. 2013;189(4 Suppl):e323.Google Scholar
- 42.Scher HI, Heller G, Molina A, et al. Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): planned final analysis (FA) of COU-AA-301, a randomized, double-blind, placebo-controlled, phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel [abstract no. LBA4517]. J Clin Oncol. 2011;29(18 Suppl 2).Google Scholar
- 43.Goodman OB, Flaig TW, Molina A, et al. Exploratory analysis of the visceral disease (VD) patient subset in COU-AA-301, a phase III study of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) [abstract no. 14]. J Clin Oncol. 2013;31(Suppl 6).Google Scholar
- 44.European Medicines Agency. Assessment report: Zytiga (abiraterone); 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/002321/WC500137814.pdf (Accessed 11 Nov 2013).
- 45.Rathkopf DE, Smith MR, de Bono JS, et al. Long-term safety and efficacy analysis of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy (COU-AA-302) [abstract no. 5009]. J Clin Oncol. 2013;31(15 Suppl 1).Google Scholar
- 46.Heidenreich A, Bolla M, Joniau S, et al. Guidelines on prostate cancer; 2011. http://www.uroweb.org/gls/pdf/08_Prostate_Cancer.pdf (Accessed 11 Nov 2013).
- 47.European Medicines Agency. Xtandi 40 mg soft capsules: summary of product characteristics; 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002639/WC500144996.pdf (Accessed 11 Nov 2013).
- 48.Astellas Pharma US Inc. XTANDI® (enzalutamide) capsules for oral use: prescribing information; 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203415lbl.pdf (Accessed 11 Nov 2013).
- 55.National Institute for Health and Clinical Excellence. Abiraterone for castration-resistant metastatic prostate cancer previously treated with a docetaxel-containing regimen (NICE technology appraisal guidance 259); 2012. http://guidance.nice.org.uk/TA259/Guidance/pdf/English (Accessed 11 Nov 2013).