Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multi-arm, multi-stage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 yrs after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomized patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards & flexible parametric models, adjusted for baseline stratification factors. 1003 patients were contemporaneously randomized (Nov-2011--Jan-2014): median age 67 yr; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% un-assessable; median PSA 97 ng/mL. At 6.1 yr median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0·60 (95%CI:0·50-0·71; P = 0.31x10-9 ) favoured SOC + AAP, with 5-yr survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0·55; 95%CI:0·41-0·76) and high-risk (HR = 0·54; 95%CI:0·43-0·69) patients. Median and current maximum time on SOC + AAP was 2.4 yr and 8.1 yr. Toxicity at 4 yr post-randomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group. This article is protected by copyright. All rights reserved.
International journal of cancer. 2022 Apr 12 [Epub ahead of print]
Nicholas D James, Noel W Clarke, Adrian Cook, Adnan Ali, Alex P Hoyle, Gert Attard, Chris D Brawley, Simon Chowdhury, William R Cross, David P Dearnaley, Johann S de Bono, Carlos Diaz Montana, Duncan Gilbert, Silke Gillessen, Clare Gilson, Rob J Jones, Ruth E Langley, Zafar I Malik, David J Matheson, Robin Millman, Chris C Parker, Cheryl Pugh, Hannah Rush, J Martin Russell, Dominic R Berthold, Michelle L Buckner, Malcolm D Mason, Alastair Ws Ritchie, Alison J Birtle, Susannah J Brock, Prantik Das, Dan Ford, Joanna Gale, Warren Grant, Emma K Gray, Peter Hoskin, Mohammad M Khan, Caroline Manetta, Neil J McPhail, Joe M O'Sullivan, Omi Parikh, Carla Perna, Carmel J Pezaro, Andrew S Protheroe, Angus J Robinson, Sarah M Rudman, Denise J Sheehan, Narayanan N Srihari, Isabel Syndikus, Jacob Tanguay, Carys W Thomas, Salil Vengalil, John Wagstaff, James P Wylie, Mahesh Kb Parmar, Matthew R Sydes
Institute of Cancer Research, London, UK., The Departments of Surgery & Urology, The Christie & Salford Royal Hospitals, Manchester, UK., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, UCL, London, UK., The Christie NHS Foundation Trust, Manchester, UK., Salford Royal HS Foundation Trust, Manchester, UK., UCL Cancer Institute, University College London, London, UK., Guy's, King's, and St. Thomas' Hospitals, and Sarah Cannon Research Institute, London, UK., St James University Hospital, Leeds, UK., The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK., Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland., Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK., The Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, UK., University of Wolverhampton, Wolverhampton, UK., (PPI) c/o MRC CTU at UCL., Royal Marsden Hospital and Institute of Cancer Research, Sutton, UK., Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; Beatson West of Scotland Cancer Centre, Glasgow, UK., Centre Hospitalier Universitaire Vaudois (CHUV), Switzerland., Velindre Hospital, Cardiff, UK., Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK., Rosemere Cancer Centre, Lancashire Teaching Hospitals, University of Manchester, University of Central Lancashire, UK., University Hospital Dorset, UK., University Hospitals of Derby and Burton NHS Foundation Trust., City Hospital, Cancer Centre at Queen Elizabeth Hospital, Birmingham., Portsmouth Hospitals University Trust, Portsmouth, UK., Gloucestershire Oncology Centre, Cheltenham General Hospital, UK., Musgrove Park Hospital, Taunton, UK., Mount Vernon Cancer Centre, Northwood, UK., Department of Oncology Castle Hill Hospital, Hull, UK., Brighton and Sussex University Hospitals NHS Trust, Brighton, UK., Raigmore Hospital, Inverness, UK., Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, UK., Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Trust, UK., Royal Surrey NHS Foundation Trust, Guildford, UK., Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK., Oxford University Hospitals NHS Foundation Trust., Sussex Cancer Centre, Brighton., Guy's & St Thomas' NHS Foundation Trust, London, UK., Royal Devon & Exeter NHS Foundation Trust, Exeter, UK., Shrewsbury & Telford Hospitals NHS Trust., Velindre Cancer Centre, Cardiff., Kent Oncology Centre, UK., University Hospital North Midlands NHS Trust., Swansea University and the South West UK Cancer Centre.