• N W Clarke, A Ali, F C Ingleby, A Hoyle, C L Amos, G Attard, C D Brawley, J Calvert, S Chowdhury, A Cook, W Cross, D P Dearnaley, H Douis, D Gilbert, S Gillessen, R J Jones, R E Langley, A MacNair, Z Malik, M D Mason, D Matheson, R Millman, C C Parker, A W S Ritchie, H Rush, J M Russell, J Brown, S Beesley, A Birtle, L Capaldi, J Gale, S Gibbs, A Lydon, A Nikapota, A Omlin, J M O'Sullivan, O Parikh, A Protheroe, S Rudman, N N Srihari, M Simms, J S Tanguay, S Tolan, J Wagstaff, J Wallace, J Wylie, A Zarkar, M R Sydes, Parmar M K B MKB MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London., and N D James.
• Department of Urology, The Christie and Salford Royal NHS Foundation Trusts, Manchester. Electronic address: noel.clarke@christie.nhs.uk.
• Ann. Oncol. 2019 Dec 1; 30 (12): 1992-2003.

BackgroundSTAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.MethodsWe randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.ResultsBetween 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).ConclusionsThe clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

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