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 et al (show 37 more authors)
(2022)
Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.
JNCI cancer spectrum, 6 (4).
pkac043-pkac043.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Prostatic Neoplasms, Androgen Antagonists, Prostate-Specific Antigen, Androgens, Male, Docetaxel |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 30 Jan 2024 11:05 |
| Last Modified: | 30 Jan 2024 11:37 |
| DOI: | 10.1093/jncics/pkac043 |
| Open Access URL: | https://doi.org/10.1093/jncics/pkac043 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178126 |
Dimensions
Dimensions
