Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.
Date
2022-07-01Author
James, ND
Ingleby, FC
Clarke, NW
Amos, CL
Attard, G
Brawley, CD
Chowdhury, S
Cross, W
Dearnaley, DP
Gilbert, DC
Gillessen, S
Jones, RJ
Langley, RE
Macnair, A
Malik, ZI
Mason, MD
Matheson, DJ
Millman, R
Parker, CC
Rush, HL
Russell, JM
Au, C
Ritchie, AWS
Mestre, RP
Ahmed, I
Birtle, AJ
Brock, SJ
Das, P
Ford, VA
Gray, EK
Hughes, RJ
Manetta, CB
McLaren, DB
Nikapota, AD
O'Sullivan, JM
Perna, C
Peedell, C
Protheroe, AS
Sundar, S
Tanguay, JS
Tolan, SP
Wagstaff, J
Wallace, JB
Wylie, JP
Zarkar, A
Parmar, MKB
Sydes, MR
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Androgen Antagonists
Androgens
Docetaxel
Humans
Male
Prostate-Specific Antigen
Prostatic Neoplasms
Research team
Prostate & Bladder Cancer
Clinic Acad RT Dearnaley
Language
eng
Date accepted
2022-02-24
License start date
2022-07-01
Citation
JNCI Cancer Spectrum, 2022, 6 (4), pp. pkac043 -
Publisher
OXFORD UNIV PRESS