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Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer.

Publication ,  Journal Article
Shore, ND; Saad, F; Cookson, MS; George, DJ; Saltzstein, DR; Tutrone, R; Akaza, H; Bossi, A; van Veenhuyzen, DF; Selby, B; Fan, X; Kang, V ...
Published in: N Engl J Med
June 4, 2020

BACKGROUND: Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known. METHODS: In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients. RESULTS: A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88). CONCLUSIONS: In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

June 4, 2020

Volume

382

Issue

23

Start / End Page

2187 / 2196

Location

United States

Related Subject Headings

  • Testosterone
  • Pyrimidinones
  • Prostatic Neoplasms
  • Phenylurea Compounds
  • Middle Aged
  • Male
  • Leuprolide
  • Injections, Subcutaneous
  • Humans
  • Gonadotropin-Releasing Hormone
 

Citation

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Shore, N. D., Saad, F., Cookson, M. S., George, D. J., Saltzstein, D. R., Tutrone, R., … HERO Study Investigators, . (2020). Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med, 382(23), 2187–2196. https://doi.org/10.1056/NEJMoa2004325
Shore, Neal D., Fred Saad, Michael S. Cookson, Daniel J. George, Daniel R. Saltzstein, Ronald Tutrone, Hideyuki Akaza, et al. “Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer.N Engl J Med 382, no. 23 (June 4, 2020): 2187–96. https://doi.org/10.1056/NEJMoa2004325.
Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187–96.
Shore, Neal D., et al. “Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer.N Engl J Med, vol. 382, no. 23, June 2020, pp. 2187–96. Pubmed, doi:10.1056/NEJMoa2004325.
Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B, HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187–2196.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

June 4, 2020

Volume

382

Issue

23

Start / End Page

2187 / 2196

Location

United States

Related Subject Headings

  • Testosterone
  • Pyrimidinones
  • Prostatic Neoplasms
  • Phenylurea Compounds
  • Middle Aged
  • Male
  • Leuprolide
  • Injections, Subcutaneous
  • Humans
  • Gonadotropin-Releasing Hormone