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Docetaxel for nonmetastatic prostate cancer: long-term survival outcomes in the STAMPEDE randomized controlled trial
James, N. D. Ingleby, F. C. Amos, C. Attard, G. Brawley, C. D. Chowdhury, S. Cross, W. Dearnaley, D. P. Gilbert, D. C.
James, N. D.
Ingleby, F. C.
Amos, C.
Attard, G.
Brawley, C. D.
Chowdhury, S.
Cross, W.
Dearnaley, D. P.
Gilbert, D. C.
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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.
Authors
James, N. D.
Ingleby, F. C.
Clarke, Noel W
Amos, C.
Attard, G.
Brawley, C. D.
Chowdhury, S.
Cross, W.
Dearnaley, D. P.
Gilbert, D. C.
Gillessen, S.
Jones, R. J.
Langley, R. E.
Macnair, A.
Malik, Z. I.
Mason, M. D.
Matheson, D. J.
Millman, R.
Parker, C. C.
Rush, H. L.
Russell, J. M.
Au, C.
Ritchie, A. W. S.
Mestre, R. P.
Ahmed, I.
Birtle, A. J.
Brock, S. J.
Das, P.
Ford, V. A.
Gray, E. K.
Hughes, R. J.
Manetta, C. B.
McLaren, D. B.
Nikapota, A. D.
O'Sullivan, J. M.
Perna, C.
Peedell, C.
Protheroe, A. S.
Sundar, S.
Tanguay, J. S.
Tolan, S. P.
Wagstaff, J.
Wallace, J. B.
Wylie, James P
Zarkar, A.
Parmar, M. K. B.
Sydes, M. R.
Ingleby, F. C.
Clarke, Noel W
Amos, C.
Attard, G.
Brawley, C. D.
Chowdhury, S.
Cross, W.
Dearnaley, D. P.
Gilbert, D. C.
Gillessen, S.
Jones, R. J.
Langley, R. E.
Macnair, A.
Malik, Z. I.
Mason, M. D.
Matheson, D. J.
Millman, R.
Parker, C. C.
Rush, H. L.
Russell, J. M.
Au, C.
Ritchie, A. W. S.
Mestre, R. P.
Ahmed, I.
Birtle, A. J.
Brock, S. J.
Das, P.
Ford, V. A.
Gray, E. K.
Hughes, R. J.
Manetta, C. B.
McLaren, D. B.
Nikapota, A. D.
O'Sullivan, J. M.
Perna, C.
Peedell, C.
Protheroe, A. S.
Sundar, S.
Tanguay, J. S.
Tolan, S. P.
Wagstaff, J.
Wallace, J. B.
Wylie, James P
Zarkar, A.
Parmar, M. K. B.
Sydes, M. R.
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Date
2022
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Article
Citation
James ND, Ingleby FC, Clarke NW, Amos C, Attard G, Brawley CD, et al. Docetaxel for nonmetastatic prostate cancer: long-term survival outcomes in the STAMPEDE randomized controlled trial. JNCI cancer spectrum. 2022 Jul 25;6(4). PubMed PMID: 35877084. Epub 2022/07/26. eng.