Enzalutamide in systemic treatment of prostate cancer
Abstract
Prostate cancer is one of the most common tumours in the human population and the most frequently diagnosed among genitourinary tumours. Despite relatively high efficacy of systemic treatment in prostate cancer, it is still one of the most important causes of premature cancer mortality in men. There are several causes of this phenomenon. One of the most important reasons for such are complications of disease spread and localisation of metastatic lesions. Others include complications related to implemented treatment, especially if chemotherapy is being administered. However, it is still the specific biological transformation and tumour evolution into state of resistance to castration (CRPC), which develops with time and under hormonal therapy, that is the major clinical challenge. Progress in the field of molecular biology enabled identification of the crucial role of signal transduction pathway dependent on the androgen receptor (AR) in CRPC. Enzalutamide is the first anti-androgen that interferes with the mechanism of progression related to AR gene amplification and/or AR over-expression. The results of the PREVAIL phase 3 trial in a population of men with metastatic CRPC not previously exposed to docetaxel were presented at ASCO GU 2014. These data prove a significant advantage of enzalutamide use over placebo in regard to all study end-points.
Enzalutamide is a drug that prolongs progression-free survival and overall survival in different populations of men with CRPC.
Keywords: castration-resistant prostate cancerandrogen receptorenzalutamide
References
- Attard G, Cooper CS, de Bono JS. Steroid hormone receptors in prostate cancer: a hard habit to break? Cancer Cell. 2009; 16(6): 458–462.
- Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009; 324(5928): 787–790.
- Hu R, Denmeade SR, Luo J. Molecular processes leading to aberrant androgen receptor signaling and castration resistance in prostate cancer. Expert Rev Endocrinol Metab. 2010; 5(5): 753–764.
- Scher HI, Fizazi K, Saad F, et al. AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012; 367(13): 1187–1197.
- Beer TM. ASCO-GU 2014. Prezentacja ustna. Clinical Trials.gov identifier: NCT01212991.
- Armstrong AJ, Lin P, Higano CS, et al. PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014; 371(5): 424–433.
- Beer TM, Armstrong AJ, Rathkopf D, et al. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study. Eur Urol. 2017; 71(2): 151–154.
- Hussain M, Fizazi K, Saad F, et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018; 378(26): 2465–2474.
- Shore ND, Chowdhury S, Villers A, et al. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol. 2016; 17(2): 153–163.
- Loriot Y, Miller K, Sternberg CN, et al. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol. 2015; 16(5): 509–521.
- Tannock I, Wit Rde, Berry W, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med. 2004; 351(15): 1502–1512.
- de Bono JS, Oudard S, Ozguroglu M, et al. TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010; 376(9747): 1147–1154.
- Crawford ED, Petrylak DP, Higano CS, et al. IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010; 363(5): 411–422.
- Li T, Thompson M, Todd M, et al. An indirect treatment comparison (ITC) and cost-effectiveness analysis of abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC) post-chemotherapy. Journal of Clinical Oncology. 2014; 32(4_suppl): 270–270.
- Fang M, Nakazawa M, Antonarakis ES, et al. Efficacy of Abiraterone and Enzalutamide in Pre- and Postdocetaxel Castration-Resistant Prostate Cancer: A Trial-Level Meta-Analysis. Prostate Cancer. 2017; 2017: 8560827.