Publication
Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy
Journal Paper/Review - Jun 3, 2017
STAMPEDE Investigators, McPhail Neil, McKinna Fiona, Malik Zafar I, Lester Jason F, Hoskin Peter J, Hingorani Mohan, Gray Emma, Gale Joanna, Ferguson Catherine, Chakraborti Prabir, Money-Kyrle Julian, O'Sullivan Joe, Sydes Matthew R, Parmar Mahesh K B, Zarkar Anjali, Wylie James, Wagstaff John, Thomas Carys, Srihari Narayanan N, Robinson Angus, Protheroe Andrew, Parikh Omi, Brock Susannah, Bowen Jo, Matheson David, Jones Rob J, Gilson Clare, Amos Claire L, Ritchie Alastair W S, Dearnaley David P, Mason Malcolm D, Clarke Noel W, Spears Melissa R, de Bono Johann S, Millman Robin, Attard Gerhardt, Birtle Alison J, Aung San, Adab Fawzi, Brawley Chris, Berthold Dominik R, Russell J Martin, Parker Christopher C, Gillessen Sommer Silke, Cross William R, Chowdhury Simon, James Nicholas D
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
Brief description/objective
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 .).