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Adding abiraterone for men with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): Survival results from STAMPEDE (NCT00268476)
Nicholas D. James, Johann S. De Bono, Melissa Ruth Spears, Noel Clarke, Malcolm David Mason, David P. Dearnaley, et al.
Editorial comment from Prof. Piotr Chlosta:
The most recent data from STAMPEDE demonstrated clinically and statistically significant effect on overall survival (OS) and failure-free survival (FFS) from adding abiraterone acetate (AA) at a start of androgen deprivation therapy (ADT) in patients with high risk locally advanced or metastatic prostate cancer. These results, together with the results of LATITUDE, support early addition of abiraterone to ADT, and are likely to be practice-changing.
Abiraterone showed a survival advantage in men with castration-refractory prostate cancer. We assessed whether abiraterone would work earlier in the disease. STAMPEDE is a randomized controlled trial using a multi-arm multi-stage platform design. It recruits patients (pts) with high-risk locally advanced or metastatic PCa starting long-term ADT. We report the first comparative survival data.
The standard-of-care (SOC) was ADT for 2+yrs; radiotherapy (RT) was mandated for men with N0M0 disease & encouraged for N+M0. Stratified randomization allocated pts 1:1 to SOC or SOC+abiraterone 1000mg + prednisolone 5mg daily. Treatment duration depended on stage & intent to give radical RT: pts not having RT or M1 disease, treatment continued until PSA, radiological & clinical progression; otherwise treatment continued until the earlier of 2 years or all types of progression. The primary outcome measure was death from any cause. Comparison to control for survival had 90% power at 2.5% 1-sided alpha for hazard ratio (HR) of 0.75, requiring ~267 control arm deaths, accounting for 3 intermediate lack-of-benefit analyses on failure-free survival (FFS). Analyses used Cox proportional hazards & flexible parametric models, adjusted for stratification factors.
1,917 pts were contemporaneously randomized to these arms (Nov 2011- Jan 2014). Groups were balanced: median age 67yrs; 52% metastatic, 20% N+/X M0, 28% N0M0; 95% newly-diagnosed; median PSA 53ng/ml. Median follow-up was 40m. There were 262 control arm deaths (82% PCa). The adjusted HR = 0.63 (95% CI 0.52-0.76; p=0.115x10-7; 184 deaths) for SOC+Abi vs SOC, with 3yr OS improved from 76% to 83%. There were 535 control arm FFS events; the adjusted HR = 0.29 (95% CI 0.25-0.34; p = 0.377x10-63, 248 FFS events) for SOC+Abi vs SOC. Grade 3 & 4 adverse events were seen in 29% & 3% SOC, 41% & 5% SOC+Abi; Grade 5: 3 & 9 (1 & 2 related).
The results show a clinically & statistically significant effect on overall survival & failure-free survival from adding abiraterone at start of ADT with a manageable increase in toxicity. ADT (+/- RT) + abiraterone is a new standard of care for this group. Clinical trial information: NCT00268476
© 2017 American Society of Clinical Oncology (ASCO).