Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial
Nicholas D. James, Fiona C. Ingleby, Noel W. Clarke, Claire Amos, Gerhardt Attard, Chris Brawley, Simon Chowdhury, William Cross, David P. Dearnaley, Duncan C. Gilbert, Silke Gillessen, Robert J. Jones, Ruth E. Langley, Archie Macnair, Zafar Malik, Malcolm D. Mason, David Matheson, Robin Millman, Chris Parker, Hannah Rush, John M. Russell, Carly Au, A.W.S. Ritchie, Ricardo Pereira Mestre, Imtiaz Ahmed, Alison Birtle, Susannah Brock, Prantik Das, Victoria A Ford, Emma Gray, Robert Hughes, Caroline Manetta, Duncan B. McLaren, Ashok Nikapota, Joe M. O’Sullivan, Carla Perna, C. Peedell, Andrew Protheroe, Santhanam Sundar, Jacob Tanguay, Shaun Tolan, John Wagstaff, Jan Wallace, James Wylie, Anjali Zarkar, Mahesh KB Parmar, Matthew R. Sydes
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.