Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy

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 de- fined 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 non- metastatic 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 were 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.) 

The authors’ full names and academic degrees are as follows: Nicholas D. James, Ph.D., Johann S. de Bono, Ph.D., Melissa R. Spears, M.Sc., Noel W. Clarke, Ch.M., Malcolm D. Mason, F.R.C.R., David P. Dearnaley, F.R.C.R., Alastair W.S. Ritchie, M.D., Claire L. Amos, Ph.D., Clare Gilson, M.R.C.P., Rob J. Jones, M.B., Ch.B., David Matheson, Ph.D., Robin Millman, Gerhardt Attard, M.D., Simon Chow- dhury, Ph.D., William R. Cross, F.R.C.S., Silke Gillessen, M.D., Christopher C. Parker, M.D., J. Martin Russell, F.R.C.R., Dominik R. Berthold, M.D., Chris Brawley, M.Sc., Fawzi Adab, F.R.C.R., San Aung, M.R.C.P., Alison J. Birtle, F.R.C.R., Jo Bowen, F.R.C.R., Susan- nah Brock, F.R.C.R., Prabir Chakraborti, F.R.C.R., Catherine Ferguson, F.R.C.R., Joanna Gale, B.M., Emma Gray, F.R.C.R., Mohan Hingorani, Ph.D., Peter J. Hoskin, F.R.C.R., Jason F. Lester, F.R.C.R., Zafar I. Malik, F.R.C.R., Fiona McKinna, F.R.C.R., Neil McPhail, F.R.C.R., Julian Money-Kyrle, F.R.C.R., Joe O’Sullivan, Ph.D., Omi Parikh, F.R.C.R., Andrew Protheroe, F.R.C.P., Angus Robinson, F.R.C.R., Narayanan N. Srihari, F.R.C.R., Carys Thomas, M.R.C.P., John Wagstaff, Ch.B., James Wylie, F.R.C.R., Anjali Zarkar, F.R.C.R., Mahesh K.B. Parmar, D.Phil., and Matthew R. Sydes, M.Sc. 

The authors’ affiliations are as follows: Institute of Cancer and Genomic Sciences, University of Birmingham (N.D.J.), and Univer- sity Hospital Birmingham (A.Z.), Birmingham, the Institute of Cancer Research (J.S.B., D.P.D., G.A.), Medical Research Council Clini- cal Trials Unit at University College London (M.R. Spears, C.L.A., C.G., C.B., M.K.B.P., M.R. Sydes), King’s College London and Guy’s and St. Thomas’ NHS Foundation Trust (S.C.), and Royal Marsden NHS Foundation Trust (C.C.P.), London, Salford Royal NHS Foun- dation Trust, Salford (N.W.C.), Cardiff University School of Medicine (M.D.M.) and Velindre Cancer Centre (J.F.L.), Cardiff, Glouces- tershire Royal Hospital (A.W.S.R.) and Gloucestershire Hospitals NHS Foundation Trust (J.B.), Gloucester, University of Glasgow, Glasgow (R.J.J., J.M.R.), St. James’s University Hospital, Leeds (W.R.C.), University Hospital of North-Midlands, Stoke-on-Trent (F.A.), Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter (S.A.), Rosemere Cancer Centre, Royal Preston Hospital, Preston (A.J.B.), Dorset Cancer Centre, Poole Hospital, Poole (S.B.), Royal Derby Hospital, Derby (P.C.), Weston Park Hospital, Sheffield (C.F.), Portsmouth Oncology Centre, Queen Alexandra Hospital, Portsmouth (J.G.), Musgrove Park Hospital, Taunton (E.G.), Hull and East Yorkshire Hospitals NHS Trust, Hull (M.H.), Mount Vernon Cancer Centre, Northwood (P.J.H.), Clatterbridge Cancer Centre, Wirral (Z.I.M.), Brighton and Sussex University Hospitals NHS Trust (F.M.) and Sussex Cancer Centre, Royal Sussex County Hospital (A.R.), Brighton, NHS Highland, Inverness (N.M.), Royal Surrey County Hospital, Guildford (J.M.-K.), Northern Ireland Cancer and Queens University, Belfast (J.O.), Lancashire Teaching Hospitals NHS Trust, Preston (O.P.), Churchill Hospital, Oxford (A.P.), Shrewsbury and Telford Hospitals NHS Trust, Shrewsbury (N.N.S.), East Kent Hospitals NHS Trust, Canterbury (C.T.), Swansea University College of Medicine, Swansea (J. Wagstaff), and Christie NHS Foundation Trust, Manchester (J. Wylie) — all in the United Kingdom; and the Department of Medical Oncology, Kantonsspital St. Gallen, St. Gallen (S.G.), and University Hospital of Lausanne, Lausanne (D.R.B.) — both in Switzerland. Two of the authors (D.M., R.M.) were unaffiliated lay members of the STAMPEDE investigators.

ASCO 2017 Presentation of STAMPEDE Trial