Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. (27th September 2019)

• Record Type: Journal Article
• Authors: Clarke, N W; Ali, A; Ingleby, F C; Hoyle, A; Amos, C L; Attard, G; Brawley, C D; Calvert, J; Chowdhury, S; Cook, A; Cross, W; Dearnaley, D P; Douis, H; Gilbert, D; Gillessen, S; Jones, R J; Langley, R E; MacNair, A; Malik, Z; Mason, M D; Matheson, D; Millman, R; Parker, C C; Ritchie, A W S; Rush, H; Russell, J M; Brown, J; Beesley, S; Birtle, A; Capaldi, L; Gale, J; Gibbs, S; Lydon, A; Nikapota, A; Omlin, A; O'Sullivan, J M; Parikh, O; Protheroe, A; Rudman, S; Srihari, N N; Simms, M; Tanguay, J S; Tolan, S; Wagstaff, J; Wallace, J; Wylie, J; Zarkar, A; Sydes, M R; Parmar, M K B; James, N D;
• Is Part Of: Annals of oncology. Volume 30:Number 12(2019)
• Page Start: 1992
• Page End: 2003
• Publication Date: 2019-09-27
• Subjects: prostate cancer -- metastatic -- hormone naive -- docetaxel -- STAMPEDE trial -- randomised control trial; Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdz396
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: Background: STAMPEDE 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. Methods: We 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. Results: Between 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). Conclusions: The 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.