Docetaxel for hormone-naïve prostate cancer (PCa): Results from long-term follow-up of non-metastatic (M0) patients in the STAMPEDE randomised trial

Abstract Background STAMPEDE previously reported that adding upfront docetaxel (Doc) improved overall survival (OS) for locally advanced and metastatic patients (pts) starting long-term androgen deprivation therapy (ADT). We report the long-term outcomes for M0 pts using metastatic progression-free survival (mPFS) as primary outcome, previously shown to be a surrogate for OS in M0 pts. Methods Standard-of-care (SOC) was ADT +/- radical radiotherapy (RT) to the prostate. 460 SOC and 230 SOC+Doc pts were recruited with 2:1 randomised stratified allocation. Standard survival intention-to-treatment analysis methods used Cox regression models adjusted for all stratification factors, with emphasis on restricted mean survival time (RMST) for non-proportional (non-PH) hazards. There was 70% power (2-sided α = 0.05) to detect HR = 0.70 for mPFS (= new metastases, skeletal related events or PCa death). Secondary outcome measures included failure free survival (FFS) and progression free survival (PFS = mPFS or locoregional progression). Results Median follow-up was ∼6.5yr compared to ∼3.5yr when last reported, with 142 mPFS events (a 54% increase) on SOC. There was no good evidence of an advantage of SOC+Doc over SOC on mPFS (HR = 0.89, 95% CI 0.66-1.19, P = 0.425); with 5yr mPFS 82% in SOC+Doc vs. 77% SOC. Secondary outcomes showed evidence that SOC+Doc improved FFS (HR = 0.70, 95% CI 0.55-0.88, P = 0.002) and PFS (non-PH P = 0.033, RMST difference=5.8 months, 95% CI 0.5-11.2, P = 0.031). There was no good evidence of a benefit of SOC+Doc on OS (125 SOC deaths; HR = 0.88, 95% CI 0.64-1.21, P = 0.442). There was no evidence that SOC+Doc increased late toxicity compared to SOC: after 1yr, G3-5 toxicity reported for 29% SOC and 30% SOC+Doc. The impact of SOC RT (nominated prior to randomisation) with and without SOC+Doc will also be detailed by subgroup. Conclusions There is robust evidence SOC+Doc improves FFS and PFS (which we have previously shown increases Quality Adjusted Life Years). There is however no good evidence that this translates into benefit for longer-term outcomes (OS or mPFS). The benefits of upfront SOC+Doc for improved FFS and PFS with no excess late toxicity may contribute to treatment discussions. Clinical trial identification NCT00268476. Legal entity responsible for the study University College London. Funding Cancer Research UK; Sanofi; MRC; Astellas; Clovis; Janssen; Novartis; Pfizer. Disclosure N.D. James: Advisory / Consultancy: Sanofi; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen. N.W. Clarke: Advisory / Consultancy: Janssen. G. Attard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Medivation; Advisory / Consultancy: Novartis; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Abbott Laboratories; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Essa Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Bayer Healthcare Pharmaceuticals; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Sanofi-Aventis; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Arno Therapeutics; Research grant / Funding (self): Innocrin Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen; Advisory / Consultancy: Veridex; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche/Ventana; Advisory / Consultancy, Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), I was an employee of the ICR, where abiraterone acetate was developed, up to 8 January 2018. : The Institute of Cancer Research (ICR). W. Cross: Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer. D. Dearnaley: Research grant / Funding (institution), Financial Support for Trial Recruitment: UK National Institute for Health Research Clinical Research Network (NIHR CRN); Research grant / Funding (institution): The Institute of Cancer Research (ICR); Research grant / Funding (self), C46/A3976, C46/A10588 and C33589/A19727. : Cancer Research UK; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Sandoz; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen. R. Jones: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. M.D. Mason: Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Bayer. C. Parker: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self): AAA; Speaker Bureau / Expert testimony: Janssen. M.K. B. Parmar: Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Astellas; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Clovis Oncology; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Novartis; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Pfizer; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Sanofi. M.R. Sydes: Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Astellas; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Clovis Oncology; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Novartis; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Janssen; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Sanofi. All other authors have declared no conflicts of interest.