Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.
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Date
2019-12-01Author
Clarke, NW
Ali, A
Ingleby, FC
Hoyle, A
Amos, CL
Attard, G
Brawley, CD
Calvert, J
Chowdhury, S
Cook, A
Cross, W
Dearnaley, DP
Douis, H
Gilbert, D
Gillessen, S
Jones, RJ
Langley, RE
MacNair, A
Malik, Z
Mason, MD
Matheson, D
Millman, R
Parker, CC
Ritchie, AWS
Rush, H
Russell, JM
Brown, J
Beesley, S
Birtle, A
Capaldi, L
Gale, J
Gibbs, S
Lydon, A
Nikapota, A
Omlin, A
O'Sullivan, JM
Parikh, O
Protheroe, A
Rudman, S
Srihari, NN
Simms, M
Tanguay, JS
Tolan, S
Wagstaff, J
Wallace, J
Wylie, J
Zarkar, A
Sydes, MR
Parmar, MKB
James, ND
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
Humans
Prostatic Neoplasms
Neoplasm Metastasis
Disease Progression
Androgen Antagonists
Antineoplastic Combined Chemotherapy Protocols
Proportional Hazards Models
Retrospective Studies
Aged
Middle Aged
Male
Docetaxel
Progression-Free Survival
Research team
Clinical Academic Radiotherapy (Dearnaley)
Treatment Resistance
Prostate and Bladder Cancer Research
Language
eng
License start date
2019-12
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2019, 30 (12), pp. 1992 - 2003
Publisher
OXFORD UNIV PRESS