Drugs & Aging

, Volume 32, Issue 3, pp 243–249 | Cite as

Enzalutamide: A Review of Its Use in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer

  • Gillian M. Keating
Adis Drug Evaluation


Enzalutamide (Xtandi®) is an androgen receptor inhibitor that blocks several steps in the androgen receptor signalling pathway. This article reviews the clinical efficacy and tolerability of oral enzalutamide in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (CRPC), as well as summarizing its pharmacological properties. In the randomized, double-blind, multinational PREVAIL trial, enzalutamide significantly improved both radiographic progression-free survival and overall survival versus placebo in chemotherapy-naïve men with metastatic CRPC who were asymptomatic or mildly symptomatic. In addition, enzalutamide significantly delayed the need for chemotherapy and the decline in health-related quality of life versus placebo. Enzalutamide was generally well tolerated in chemotherapy-naïve men with metastatic CRPC. In conclusion, enzalutamide is a convenient, effective and well tolerated treatment for chemotherapy-naïve men with metastatic CRPC who are asymptomatic or mildly symptomatic.


Overall Survival Androgen Receptor Placebo Recipient National Comprehensive Cancer Network National Comprehensive Cancer Network 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The preparation of this review was not supported by any external funding. Gillian Keating is a salaried employee of Adis/Springer. 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.


  1. 1.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in onoclogy (NCCN guidelines): prostate cancer (version 1.2015). 2015. Accessed 9 Feb 2015.
  2. 2.
    Bastos DA, Dzik C, Rathkopf D, et al. Expanding androgen- and androgen receptor signaling-directed therapies for castration-resistant prostate cancer. Oncology. 2014;28(8):693–9.PubMedGoogle Scholar
  3. 3.
    Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324(5928):787–90.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Sanford M. Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Drugs. 2013;73(15):1723–32.CrossRefPubMedGoogle Scholar
  5. 5.
    Guerrero J, Alfaro IE, Gómez F, et al. Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. Prostate. 2013;73(12):1291–305.CrossRefPubMedGoogle Scholar
  6. 6.
    Efstathiou E, Titus M, Wen S, et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol. 2015;67(1):53–60.CrossRefPubMedGoogle Scholar
  7. 7.
    Scher HI, Beer TM, Higano CS, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study. Lancet. 2010;375(9724):1437–46.CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Ardiani A, Gameiro SR, Kwilas AR, et al. Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway. Oncotarget. 2014;5(19):9335–48.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Nakazawa M, Antonarakis ES, Luo J. Androgen receptor splice variants in the era of enzalutamide and abiraterone. Horm Cancer. 2014;5(5):265–73.CrossRefPubMedGoogle Scholar
  10. 10.
    Li Y, Chan SC, Brand LJ, et al. Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res. 2013;73(2):483–9.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Cao B, Qi Y, Zhang G, et al. Androgen receptor splice variants activating the full-length receptor in mediating resistance to androgen-directed therapy. Oncotarget. 2014;5(6):1646–56.PubMedGoogle Scholar
  12. 12.
    Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014;371(11):1028–38.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Qu Y, Dai B, Ye D, et al. Constitutively active AR-V7 plays an essential role in the development and progression of castration-resistant prostate cancer. Sci Rep. 2015;5:7654.CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Joseph JD, Lu N, Qian J, et al. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov. 2013;3(9):1020–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Balbas MD, Evans MJ, Hosfield DJ, et al. Overcoming mutation-based resistance to antiandrogens with rational drug design. Elife. 2013;2:e00499.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Korpal M, Korn JM, Gao X, et al. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov. 2013;3(9):1030–43.CrossRefPubMedGoogle Scholar
  17. 17.
    Arora VK, Schenkein E, Murali R, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155(6):1309–22.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Carver BS, Chapinski C, Wongvipat J, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19(5):575–86.CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Nadiminty N, Tummala R, Liu C, et al. NF-κB2/p52 induces resistance to enzalutamide in prostate cancer: role of androgen receptor and its variants. Mol Cancer Ther. 2013;12(8):1629–37.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Bishop JL, Sio A, Angeles A, et al. PD-L1 is highly expressed in enzalutamide resistant prostate cancer. Oncotarget. 2014;6(1):234–42.Google Scholar
  21. 21.
    Schrader AJ, Boegemann M, Ohlmann C-H, et al. Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone. Eur Urol. 2014;65(1):30–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Bianchini D, Lorente D, Rodriguez-Vida A, et al. Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone. Eur J Cancer. 2014;50(1):78–84.CrossRefPubMedGoogle Scholar
  23. 23.
    Loriot Y, Bianchini D, Ileana E, et al. Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol. 2013;24(7):1807–12.CrossRefPubMedGoogle Scholar
  24. 24.
    Thomsen FB, Røder MA, Rathenborg P, et al. Enzalutamide treatment in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy and abiraterone acetate. Scand J Urol. 2014;48(3):268–75.CrossRefPubMedGoogle Scholar
  25. 25.
    Thomson D, Charnley N, Parikh O. Enzalutamide after failure of docetaxel and abiraterone in metastatic castrate-resistant prostate cancer. Eur J Cancer. 2014;50(5):1040–1.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhang T, Dhawan MS, Healy P, et al. Clinical benefit of docetaxel or enzalutamide after progression on first-line abiraterone acetate and prednisone in men with metastatic castration resistant prostate cancer (mCRPC) [abstract no. e16031]. J Clin Oncol. 2014;32(15 Suppl).Google Scholar
  27. 27.
    Vera-Badillo FE, Leibowitz-Amit R, Templeton A, et al. Clinical activity of enzalutamide against metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on abiraterone acetate: the Princess Margaret experience [abstract no. 159]. J Clin Oncol. 2014;32(4 Suppl).Google Scholar
  28. 28.
    Sandhu GS, Parikh RA, Appleman LJ, et al. Enzalutamide after abiraterone in patients with metastatic castrate-resistant prostate cancer (mCRPC) [abstract no. 240]. J Clin Oncol. 2014;32(4 Suppl).Google Scholar
  29. 29.
    Cheng HH, Gulati R, Azad A, et al. Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel. Prostate Cancer Prostatic Dis. 2015. doi: 10.1038/pcan.2014.53.
  30. 30.
    European Medicines Agency. Xtandi (enzalutamide): EU summary of product characteristics. 2015. Accessed 9 Feb 2015.
  31. 31.
    Astellas Pharma US Inc. Xtandi® (enzalutamide) capsules for oral use: US prescribing information. 2014. Accessed 9 Feb 2015.
  32. 32.
    Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–33.CrossRefPubMedGoogle Scholar
  33. 33.
    Evans C, Higano CS, Keane T, et al. The PREVAIL study: primary and non-visceral/visceral disease subgroup results for enzalutamide-treated men with metastatic prostate cancer (mPC) that had progressed on ADT [abstract no. PI-05 plus slide presentation]. In: 2014 Annual Meeting of the American Urological Association. 2014.Google Scholar
  34. 34.
    Higano C, Alumkal J, Chowdhury S, et al. Response rates and outcomes with enzalutamide for patients with metastatic castration resistant prostate cancer and visceral disease in the PREVAIL trial [abstract no. 767P]. Ann Oncol. 2014;25(Suppl 4):iv262.Google Scholar
  35. 35.
    Loriot Y, Miller K, Sternberg CN, et al. Impact of enzalutamide on skeletal related events (SREs), pain and quality of life (QoL) in the PREVAIL trial [abstract no. 762PD]. Ann Oncol. 2014;25(Suppl 4):iv259.Google Scholar
  36. 36.
    Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138–48.CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22.CrossRefPubMedGoogle Scholar
  38. 38.
    Janssen Biotech Inc. Zytiga® (abiraterone acetate) tablets: US prescribing information. 2015. Accessed 9 Feb 2014.
  39. 39.
    Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–97.CrossRefPubMedGoogle Scholar
  40. 40.
    Maughan BL, Antonarakis ES. Enzalutamide in chemo-naive castration-resistant prostate cancer: effective for most but not for all. Asian J Androl. 2014;16(5):807–8.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Efstathiou E, Titus MA, Wen S, et al. Enzalutamide (ENZA) in combination with abiraterone acetate (AA) in bone metastatic castration resistant prostate cancer (mCRPC) [abstract no. 5000]. J Clin Oncol. 2014;32(15 Suppl).Google Scholar
  42. 42.
    Sartor AO, Tangen CM, Hussain MH, et al. Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer. 2008;112(11):2393–400.CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Rodriguez-Vida A, Bianchini D, Van Hemelrijck M, et al. Is there an antiandrogen withdrawal syndrome with enzalutamide? BJU Int. 2014. doi: 10.1111/bju.12826.
  44. 44.
    von Klot CAJ, Kramer MW, Böker A, et al. Is there an anti-androgen withdrawal syndrome for enzalutamide? World J Urol. 2014;32(5):1171–6.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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