Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial. Issue 4 (25th July 2022)

• Record Type: Journal Article
• 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 J; Millman, Robin; Parker, Chris C; Rush, Hannah L; Russell, J Martin; Au, Carly; Ritchie, Alastair W S; 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 K B; Sydes, Matthew R;
• Is Part Of: JNCI cancer spectrum. Volume 6:Issue 4(2022)
• Publication Date: 2022-07-25
• DOI: 10.1093/jncics/pkac043
• Languages: English
• ISSNs: 2515-5091

Abstract

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.