Docetaxel for nonmetastatic prostate cancer: long-term survival outcomes in the STAMPEDE randomized controlled trial

James, N. D. et al. (2022) Docetaxel for nonmetastatic prostate cancer: long-term survival outcomes in the STAMPEDE randomized controlled trial. JNCI Cancer Spectrum, 6(4), pkac043. (doi: 10.1093/jncics/pkac043) (PMID:35877084) (PMCID:PMC9338456)

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.

• Item Type: Articles
• Additional Information: This work was supported by Cancer Research UK (grant number CRUK_A12459); Medical Research Council (grant number MRC_MC_UU_12023/25, grant number MC_UU_00004/01); Sanofi; Astellas; Clovis; Janssen; Novartis; Pfizer. NDJ, CCP, and DPD were supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jones, Professor Robert and Russell, Dr Martin
• Authors: James, N. D., Ingleby, F. C., Clarke, N. W., Amos, C. L., 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, J. P., Zarkar, A., Parmar, M. K. B., and Sydes, M. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: JNCI Cancer Spectrum
• Publisher: Oxford University Press
• ISSN: 2515-5091
• ISSN (Online): 2515-5091
• Published Online: 25 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in JNCI Cancer Spectrum 6(4): pkac043
• Publisher Policy: Reproduced under a Creative Commons License