STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy (ADT). We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally-demonstrated surrogate for overall survival.
Standard-of-care (SOC) was ADT+/-radical prostate radiotherapy (RT). 460 SOC and 230 SOC+Doc were randomized 2:1. Standard survival methods and intention-to-treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time (RMST) if non-proportional (non-PH) hazards. mPFS (new metastases, skeletal-related events or prostate cancer death) had 70% power (α = 0.05) for HR = 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS) and progression-free survival (PFS: mPFS, locoregional progression).
Median follow-up was 6.5 yr with 142 mPFS events on SOC (3 yr and 54% increases over previous report). There was no good evidence of an advantage to SOC+Doc on mPFS (HR = 0.89, 95%CI : 0.66-1.19, P = .43); with 5 yr mPFS 82% (95%CI : 78%-87%) SOC+Doc vs. 77% (95%CI : 73%-81%) SOC. Secondary outcomes showed evidence SOC+Doc improved FFS (HR = 0.70, 95%CI 0.55-0.88, P = .002) and PFS (non-PH P = .033, RMST difference = 5.8 m, 95%CI : 0.5-11.2, P = .031), but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95%CI : 0.64-1.21, P = .442). There was no evidence SOC+Doc increased late toxicity: post-1yr, 29% SOC and 30% SOC+Doc G3-5 toxicity.
There is robust evidence SOC+Doc improved FFS and PFS (previously shown to increase Quality-Adjusted-Life-Years), without excess late toxicity, which did not translates into benefit for longer-term outcomes. This may influence patient management in individual cases.
NCT00268476.
JNCI cancer spectrum. 2022 Jul 25 [Epub ahead of print]
Nicholas D James, Fiona C Ingleby, Noel W Clarke, Claire Amos, Gerhardt Attard, Christopher D Brawley, Simon Chowdhury, William Cross, David P Dearnaley, Duncan C Gilbert, Silke Gillessen, Robert J Jones, Ruth E Langley, Archie Macnair, Zafar I Malik, Malcolm D Mason, David J Matheson, Robin Millman, Chris C Parker, Hannah L Rush, J Martin Russell, Carly Au, Alastair W S Ritchie, Ricardo Pereira Mestre, Imtiaz Ahmed, Alison J Birtle, Susannah J Brock, Prantik Das, Victoria A Ford, Emma K Gray, Robert J Hughes, Caroline B Manetta, Duncan B McLaren, Ashok D Nikapota, Joe M O'Sullivan, Carla Perna, Clive Peedell, Andrew S Protheroe, Santhanam Sundar, Jacob S Tanguay, Shaun P Tolan, John Wagstaff, Jan B Wallace, James P Wylie, Anjali Zarkar, Mahesh K B Parmar, Matthew R Sydes
The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK., The Christie and Salford Royal Hospitals, Manchester, UK., University College London Cancer Institute, London, UK., Guy's, King's, and St. Thomas' Hospitals, and Sarah Cannon Research Institute, London, UK., St James's University Hospital, Leeds, UK., Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland., Institute of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK., The Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, UK., School of Medicine, Cardiff University, UK., University of Wolverhampton, Wolverhampton, UK., c/o 2., Urology Department. Gloucestershire Royal NHS Foundation Trust, Gloucester, UK, (retired)., Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland., Southend University NHS Trust, Southend, UK., Rosemere Cancer Centre Lancashire Teaching Hospitals & University of Manchester., University Hospital Dorset, UK., University Hospitals of Derby NHS Foundation Trust, Derby, UK., Royal Devon and Exeter NHS Foundation Trust, Exeter, UK., Musgrove Park Hospital, Taunton, UK., Mount Vernon Cancer Centre, UK., Sussex Cancer Centre, Brighton and Sussex University Hospitals, Brighton, UK., Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK., Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Royal Surrey NHS Foundation Trust, Guildford, UK., James Cook University Hospital, Middlesbrough, UK., Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Nottingham University Hospitals NHS Trust, Nottingham, UK., Velindre Cancer Centre, Cardiff, UK., Swansea University College of Medicine & The South West Wales Cancer Centre., Beatson West of Scotland Cancer Centre, Glasgow, UK., The Christie NHS Foundation Trust, Manchester, UK., University Hospitals Birmingham, UK.