Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.
- Sydes MR MRC Clinical Trials Unit at UCL, London. Electronic address: mrcctu.stampede-publications@ucl.ac.uk.
- Spears MR MRC Clinical Trials Unit at UCL, London.
- Mason MD Cardiff University, Cardiff.
- Clarke NW Christie and Royal Salford Hospital, Manchester.
- Dearnaley DP Institute of Cancer Research, Sutton.
- de Bono JS Institute of Cancer Research, Sutton.
- Attard G UCL Cancer Institute, University College London, London.
- Chowdhury S Guy's & St Thomas NHS, Foundation Trust, London.
- Cross W St James University Hospital, Leeds, UK.
- Gillessen S Division of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen; University of Bern, Bern; Swiss Group for Cancer Clinical Research (SAKK), Bern, Switzerland.
- Malik ZI The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool.
- Jones R Institute of Cancer Sciences, University of Glasgow, Glasgow; Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow.
- Parker CC Institute of Cancer Research, Sutton; Royal Marsden Hospital, Sutton.
- Ritchie AWS MRC Clinical Trials Unit at UCL, London.
- Russell JM Institute of Cancer Sciences, University of Glasgow, Glasgow; Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow.
- Millman R MRC Clinical Trials Unit at UCL, London.
- Matheson D Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wolverhampton.
- Amos C MRC Clinical Trials Unit at UCL, London.
- Gilson C MRC Clinical Trials Unit at UCL, London.
- Birtle A Rosemere Cancer Centre, Royal Preston Hospital, Preston.
- Brock S Dorset Cancer Centre, Poole Hospital, Poole.
- Capaldi L Worcestershire Acute Hospitals NHS Trust, Worcester.
- Chakraborti P Royal Derby Hospital, Derby.
- Choudhury A Division of Cancer Sciences, University of Manchester, Manchester; Manchester Academic Health Science Centre, Manchester; Christie Hospital NHS Foundation Trust, Manchester.
- Evans L Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield.
- Ford D City Hospital, Cancer Centre at Queen Elizabeth Hospital, Birmingham.
- Gale J Portsmouth Oncology Centre, Queen Alexandra Hospital, Portsmouth.
- Gibbs S Queen's Hospital, Romford.
- Gilbert DC Sussex Cancer Centre, Royal Sussex County Hospital, Brighton.
- Hughes R Mount Vernon Group, Mount Vernon Hospital, Middlesex.
- McLaren D Western General Hospital, Edinburgh.
- Lester JF Velindre Cancer Centre, Cardiff.
- Nikapota A Sussex Cancer Centre, Brighton.
- O'Sullivan J Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast; Belfast City Hospital, Belfast.
- Parikh O Lancashire Teaching Hospitals NHS Trust, Preston.
- Peedell C Department of Oncology & Radiotherapy, South Tees NHS Trust, Middlesbrough.
- Protheroe A Oxford University Hospitals NHS Foundation Trust.
- Rudman SM Guy's & St Thomas NHS, Foundation Trust, London.
- Shaffer R Department of Oncology, Royal Surrey County Hospital, Guildford.
- Sheehan D Royal Devon and Exeter Hospital, Exeter.
- Simms M Hull & East Yorkshire Hospitals NHS Trust, Hull.
- Srihari N Shrewsbury and Telford Hospitals NHS Trust, Shrewsbury, UK.
- Strebel R Kantonsspital Graubünden, Chur; Swiss Group for Cancer Clinical Research (SAKK), Bern, Switzerland.
- Sundar S Department of Oncology, Nottingham, University Hospitals NHS Trust, Nottingham.
- Tolan S The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool.
- Tsang D Southend Hospital, Southend-on-Sea.
- Varughese M Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust.
- Wagstaff J Swansea University College of Medicine, Swansea.
- Parmar MKB MRC Clinical Trials Unit at UCL, London. Electronic address: mrcctu.stampede-publications@ucl.ac.uk.
- James ND Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
- 2018-03-13
Published in:
- Annals of oncology : official journal of the European Society for Medical Oncology. - 2018
Abiraterone Acetate
Aged
Androgen Antagonists
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Docetaxel
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Male
Network Meta-Analysis
Progression-Free Survival
Prostate-Specific Antigen
Prostatic Neoplasms
Standard of Care
English
Background
Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP.
Method
Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP.
Results
A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm.
Conclusions
This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.
Trial registration
Clinicaltrials.gov: NCT00268476.
Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP.
Method
Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP.
Results
A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm.
Conclusions
This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.
Trial registration
Clinicaltrials.gov: NCT00268476.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/annonc/mdy072
- PMID 29529169
- Persistent URL
- https://sonar.ch/global/documents/167185
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