Skip to main content
SpringerLink
Log in

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

  • Adis Drug Evaluation
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in onoclogy (NCCN guidelines): prostate cancer (version 1.2015). 2015. http://www.nccn.org/. Accessed 9 Feb 2015.

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Sanford M. Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Drugs. 2013;73(15):1723–32.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  15. Balbas MD, Evans MJ, Hosfield DJ, et al. Overcoming mutation-based resistance to antiandrogens with rational drug design. Elife. 2013;2:e00499.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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).

  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).

  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).

  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. European Medicines Agency. Xtandi (enzalutamide): EU summary of product characteristics. 2015. http://www.ema.europa.eu/. Accessed 9 Feb 2015.

  31. Astellas Pharma US Inc. Xtandi® (enzalutamide) capsules for oral use: US prescribing information. 2014. http://www.xtandi.com/. Accessed 9 Feb 2015.

  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.

    Article  PubMed  Google Scholar 

  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.

  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. 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. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  38. Janssen Biotech Inc. Zytiga® (abiraterone acetate) tablets: US prescribing information. 2015. http://www.zytigahcp.com/full-prescribing-information. Accessed 9 Feb 2014.

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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).

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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. 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.

    Article  Google Scholar 

Download references

Disclosure

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.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand

    Gillian M. Keating

Authors
  1. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian M. Keating.

Additional information

The manuscript was reviewed by: J. Carles, Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain; C. N. Sternberg, Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keating, G.M. Enzalutamide: A Review of Its Use in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer. Drugs Aging 32, 243–249 (2015). https://doi.org/10.1007/s40266-015-0248-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-015-0248-y

Keywords

Search

Navigation