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Docetaxel for nonmetastatic prostate cancer: Long-term survival outcomes in the STAMPEDE randomized controlled trial
James, Nicholas D Ingleby, Fiona C Clarke, Noel W Amos, Claire L. Attard, Gerhardt Brawley, Christopher D Chowdhury, Simon Cross, William Dearnaley, David P Gilbert, Duncan C
James, Nicholas D
Ingleby, Fiona C
Clarke, Noel W
Amos, Claire L.
Attard, Gerhardt
Brawley, Christopher D
Chowdhury, Simon
Cross, William
Dearnaley, David P
Gilbert, Duncan C
Authors
James, Nicholas D
Ingleby, Fiona C
Clarke, Noel W
Amos, Claire L.
Attard, Gerhardt
Brawley, Christopher D
Chowdhury, Simon
Cross, William
Dearnaley, David P
Gilbert, Duncan C
Gillessen, Silke
Jones, Robert J
Langley, Ruth E
Macnair, Archie
Malik, Zafar I
Mason, Malcolm D
Matheson, David
Millman, Robin
Parker, Chris C
Rush, Hannah L
Russell, J Martin
Au, Carly
Ritchie, Alastair WS
Mestre, Ricardo Pereira
Ahmed, Imtiaz
Birtle, Alison J
Brock, Susannah J
Das, Prantik
Ford, Victoria A
Gray, Emma K
Hughes, Robert J
Manetta, Caroline B
McLaren, Duncan B
Nikapota, Ashok D
O’Sullivan, Joe M
Perna, Carla
Peedell, Clive
Protheroe, Andrew S
Sundar, Santhanam
Tanguay, Jacob S
Tolan, Shaun P
Wagstaff, John
Wallace, Jan B
Wylie, James P
Zarkar, Anjali
Parmar, Mahesh KB
Sydes, Matthew R
Ingleby, Fiona C
Clarke, Noel W
Amos, Claire L.
Attard, Gerhardt
Brawley, Christopher D
Chowdhury, Simon
Cross, William
Dearnaley, David P
Gilbert, Duncan C
Gillessen, Silke
Jones, Robert J
Langley, Ruth E
Macnair, Archie
Malik, Zafar I
Mason, Malcolm D
Matheson, David
Millman, Robin
Parker, Chris C
Rush, Hannah L
Russell, J Martin
Au, Carly
Ritchie, Alastair WS
Mestre, Ricardo Pereira
Ahmed, Imtiaz
Birtle, Alison J
Brock, Susannah J
Das, Prantik
Ford, Victoria A
Gray, Emma K
Hughes, Robert J
Manetta, Caroline B
McLaren, Duncan B
Nikapota, Ashok D
O’Sullivan, Joe M
Perna, Carla
Peedell, Clive
Protheroe, Andrew S
Sundar, Santhanam
Tanguay, Jacob S
Tolan, Shaun P
Wagstaff, John
Wallace, Jan B
Wylie, James P
Zarkar, Anjali
Parmar, Mahesh KB
Sydes, Matthew R
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2022-07-25
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Abstract
Background STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. 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. Methods Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 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 if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression). Results Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity. Conclusions There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.
Citation
James, N.D., Ingleby, F.C., Clarke, N.W. et al. (2022) Docetaxel for nonmetastatic prostate cancer: Long-term survival outcomes in the STAMPEDE randomized controlled trial. JNCI Cancer Spectrum, 6(4), pkac043.
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Journal article
Language
en
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© 2022 The Authors. Published by OUP. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/jncics/pkac043
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ISSN
1475-4029
EISSN
1475-4029
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This work was supported by Cancer Research UK (grant number CRUK_A12459); Medical Research Council (grant number MRC_MC_UU_12023/25, grant number MC_UU_00004/01); Sanofi; Astellas; Clovis; Janssen; Novartis; Pfizer. NDJ, CCP, and DPD were supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London.