Abstract
Apalutamide (marketed as Erleada®) is an oral non-steroidal next-generation selective inhibitor of the androgen receptor (AR), and is approved in several countries, including the USA and those of the EU, for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In men with nmCRPC who were receiving androgen-deprivation therapy (ADT) and had a high risk of metastases in SPARTAN, apalutamide significantly prolonged metastasis-free survival (MFS) compared with placebo, with consistent benefits demonstrated across subgroups. The addition of apalutamide to ongoing ADT significantly prolonged time to metastasis and progression-free survival (PFS) compared with placebo, and maintained health-related quality of life (HR-QOL). Apalutamide was generally well tolerated in SPARTAN, with fatigue being the most frequently reported adverse event. Given the available evidence, apalutamide with ongoing ADT represents an emerging treatment option for patients with nmCRPC who are at high risk of developing metastatic disease.
Similar content being viewed by others
References
El-Amm J, Aragon-Ching JB. The current landscape of treatment in non-metastatic castration-resistant prostate cancer. Clin Med Insights Oncol. 2019. https://doi.org/10.1177/1179554919833927.
Esther J, Maughan BL, Anderson N, et al. Management of nonmetastatic castration-resistant prostate cancer: recent advances and future direction. Curr Treat Options Oncol. 2019. https://doi.org/10.1007/s11864-019-0611-z.
Clegg NJ, Wongvipat J, Joseph JD, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012;72(6):1494–503.
Janssen Pharmaceutical Companies. ErleadaTM (apalutamide): US prescribing information. 2018. http://www.fda.gov/. Accessed 16 Aug 2019.
European Medicines Agency. Erleada (apalutamide): EU summary of product characteristics. 2019. http://www.ema.europa.eu/. Accessed 16 Aug 2019.
Koukourakis MI, Kakouratos C, Kalamida D, et al. Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines. Anticancer Drugs. 2018;29(4):323–33.
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.
Rathkopf DE, Smith MR, Ryan CJ, et al. Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide. Ann Oncol. 2017;28(9):2264–71.
Balbas MD, Evans MJ, Hosfield DJ, et al. Overcoming mutation-based resistance to antiandrogens with rational drug design. Elife. 2013. https://doi.org/10.7554/eLife.00499.
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.
Smith MR, Thomas S, Chowdhury S, et al. Androgen receptor (AR) anomalies and efficacy of apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) from the phase 3 SPARTAN study [abstract no. 2605]. Cancer Res. 2018;78(13 Suppl).
Espaillat MP, Rajpurohit Y, Gormley M, et al. Digital droplet PCR (ddPCR)-based detection of androgen receptor splice variant 7 (AR-v7) in non-metastatic castration resistant prostate [abstract no. 1335]. In: AACR Annual Meeting 2019 Proceedings. 2019.
Feng FY, Thomas S, Gormley M, et al. Identifying molecular determinants of response to apalutamide (APA) in patients (PTS) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the SPARTAN trial [abstract no. 42]. J Clin Oncol. 2019;37(7 Suppl).
Belderbos BPSI, de Wit R, Chien C, et al. An open-label, multicenter, phase Ib study investigating the effect of apalutamide on ventricular repolarization in men with castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2018;82(3):457–68.
Rathkopf DE, Morris MJ, Fox JJ, et al. Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2013;31(28):3525–30.
Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378(15):1408–18.
Smith MR, Antonarakis ES, Ryan CJ, et al. Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastatic castration-resistant prostate cancer cohort. Eur Urol. 2016;70(6):963–70.
Janssen Research & Development. A multicenter, randomized, double-blind, placebo-controlled, phase III study of ARN509 in men with non-metastatic (M0) castration-resistant prostate cancer—selective prostate AR targeting with ARN-509 (SPARTAN): clinical study report. 2017. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/rev_210951_arn-509-003_CSR_Redacted.pdf. Accessed 22 Aug 2019.
Mainwaring P, Small E, Uemura H, et al. Efficacy and safety of apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) from SPARTAN: Asian subpopulation [abstract no. 2130]. Ann Oncol. 2018;29(Suppl 9).
Hadaschik BA, Saad F, Graff JN, et al. Efficacy and safety of apalutamide (APA) in nonmetastatic castration-resistant prostate cancer (nmCRPC) patients (pts) with or without prior radical prostatectomy (RP) and/or external radiotherapy (XRT): post hoc analysis of SPARTAN [abstract no. MP34-19]. J Urol. 2019;201(Suppl 4):e502–3.
Saad F, Thomas S, Feng FY, et al. Response to apalutamide (APA) among patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) from SPARTAN by Decipher Genomic Classifier (GC) score [abstract no. PD11-03]. J Urol. 2019;201(4 Suppl):e216.
Small EJ, Saad F, Chowdhury S, et al. Efficacy of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and baseline (BL) comorbidities (CM) [abstract no. 5023]. J Clin Oncol. 2019;37(Suppl).
Graff J, Saad F, Hadaschik BA, et al. Metastasis-free survival (MFS) in nonmetastatic castration-resistant prostate cancer (NMCRPC) patients (pts) with prostate-specific antigen (PSA) decline to < 0.2 ng/ml following apalutamide (APA) treatment: post hoc results from the phase 3 SPARTAN study [abstract no. MP34-20]. J Urol. 2019;201(Suppl 4):e503.
Small EJ, Saad F, Rathkopf DE, et al. Predicting disease progression in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): an analysis from the phase 3 SPARTAN trial [abstract no. 5034]. J Clin Oncol. 2018;36(15 Suppl).
Smith MR, Mehra M, Nair S, et al. Association of metastasis-free survival (MFS) and overall survival (OS) in nonmetastatic castration-resistant prostate cancer (nmCRPC) [abstract no. 5032]. J Clin Oncol. 2018;36(15 Suppl).
Small EJ, Saad F, Chowdhury S, et al. Updated analysis of progression-free survival with first subsequent therapy (PFS2) and safety in the SPARTAN study of apalutamide (APA) in patients (pts) with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC) [abstract no. 144]. J Clin Oncol. 2019;37(7 Suppl).
Saad F, Cella D, Basch E, et al. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(10):1404–16.
Data on file, Janssen Pharmaceutical Companies, 2019.
Pollock YY, Smith MR, Saad F, et al. Predictors of falls and fractures in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide (APA) plus ongoing androgen deprivation therapy (ADT). [abstract no. 5025]. J Clin Oncol. 2019;37(Suppl).
European Association of Urology. EAU oncology guidelines: prostate cancer. 2019. https://uroweb.org/guideline/prostate-cancer/#1. Accessed 23 Jul 2019.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: prostate cancer. 2019. http://www.nccn.org/. Accessed 16 Aug 2019.
Chowdhury S, Oudard S, Hadaschik BA, et al. Matching-adjusted indirect comparison of the efficacy of apalutamide and enzalutamide in the treatment of non-metastatic castration-resistant prostate cancer [abstract no. PCN37]. Value Health. 2018;21 (Suppl 3):S20–1.
Wallis CJD, Chandrasekar T, Goldberg H, et al. Advanced androgen blockage in nonmetastatic castration-resistant prostate cancer: an indirect comparison of apalutamide and enzalutamide. Eur Urol Oncol. 2018;1(3):238–41.
Riaz IB, Bhattacharjee S, Malik S, et al. Apalutamide (APA) or enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (CRPC): a systematic review and network meta-analysis of randomized clinical trials (RCTs) [abstract no. 263]. J Clin Oncol. 2019;37(7 Suppl).
Zhou Z, Hu X. Cost-effectiveness analysis of apalutamide for treatment in non-metastasis castration-resistant prostate cancer [abstract no. PCN153]. Value Health. 2018;21 (Suppl 3):S40–1.
Beaver JA, Kluetz PG, Pazdur R. Metastasis-free survival: a new end point in prostate cancer trials. N Engl J Med. 2018;378(26):2458–60.
Chandler R, De Bono J. Second-generation antiandrogens in nonmetastatic CRPC. Nat Rev Urol. 2018;15(6):342–4.
Gagnon R, Ali-Mohamed NS, Batuyong E, et al. Metastasis-free survival as a predictor of overall survival in non-metastatic castration-resistant prostate cancer [abstract no. 201]. J Clin Oncol. 2019;37(7 Suppl).
Schultz NM, Sugarman R, Ramaswamy K, et al. Clinical benefits and risk of enzalutamide and apalutamide: number needed to treat and number needed to harm analysis for patients with non-metastatic castration-resistant prostate cancer [abstract no. MP34-18]. J Urol. 2019;201(Suppl 4):e502.
Acknowledgements
During the peer review process, the manufacturer of apalutamide was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The preparation of this review was not supported by any external funding.
Conflicts of interest
Zaina T. Al-Salama is a salaried employee of Adis International Ltd/Springer Nature is responsible for the article content and declares no relevant conflicts of interest
Additional information
Additional information for this Adis Drug Evaluation can be found at https://doi.org/10.6084/m9.figshare.9037439.
The manuscript was reviewed by:T.M. de Reijke, Department of Urology, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands; U. Emmenegger, Sunnybrook Odette Cancer Centre, Division of Medical Oncology, University of Toronto, Toronto, ON, Canada; N. Shore, Carolina Urologic Research Center, Myrtle Beach, SC, USA.
Rights and permissions
About this article
Cite this article
Al-Salama, Z.T. Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Drugs 79, 1591–1598 (2019). https://doi.org/10.1007/s40265-019-01194-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40265-019-01194-x