Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy

James, N and de Bono, J and Spears, M and Clarke, NW and Mason, M and Dearnaley, D and Ritchie, A and Amos, C and Gilson, C and Jones, R and Matheson, DJ and Millman, R and Attard, G and Chowdhury, S and Cross, W and Gillessen, S and Parker, C and Russell, M and Berthold, D and Brawley, C and Adab, F and Aung, S and Birtle, AJ and Bowen, J and Brock, S and Chakraborti, P and Ferguson, C and Gale, J and Gray, E and Hingorani, M and Hoskin, P and Lester, J and Malik, Z and McKinna, F and McPhail, N and Money-Kyrle, J and O'Sullivan, J and Parikh, O and Protheroe, A and Robinson, A and Srihari, N and Thomas, C and Wagstaff, J and Wylie, J and Zarkar, A and Parmar, M and Sydes, M (2017) Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. The New England journal of medicine, 377 (4). pp. 338-351. ISSN 0028-4793 DOI: https://doi.org/10.1056/NEJMoa1702900

Abstract

BACKGROUND Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. METHODS We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). RESULTS A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). CONCLUSIONS Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476, and Current Controlled Trials number, ISRCTN78818544.)

More Information

Identification Number:	https://doi.org/10.1056/NEJMoa1702900
Status:	Published
Refereed:	Yes
Publisher:	Massachusetts Medical Society
Uncontrolled Keywords:	11 Medical And Health Sciences, General & Internal Medicine,
Depositing User (symplectic)	Deposited by Bayjoo, Jennifer on behalf of Matheson, David
Date Deposited:	09 Jun 2017 13:29
Last Modified:	11 Jul 2024 07:36
Item Type:	Article