Patients with high-risk prostate cancer beginning long-term androgen deprivation therapy (ADT) showed similar outcomes from the addition of abiraterone acetate plus prednisolone or docetaxel plus prednisone, according to findings from the STAMPEDE trial presented during ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain. Both treatments have shown practice-changing benefits over the previous standard of care (SOC) of first line ADT with further treatments on relapse.
Matthew R. Sydes, MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK, presented data from a subset of the STAMPEDE trial (NCT00268476), which is a multi-arm multi-stage platform randomised controlled protocol recruiting patients just beginning long-term ADT for high-risk locally-advanced or metastatic prostate cancer. Recruitment of patients for the comparison of docetaxel+prednisone plus SOC versus SOC overlapped for 16 months with recruiting patients for abiraterone acetate+prednisone plus SOC versus SOC. Data were presented on these contemporaneously randomised patients. The SOC therapy comprised long-term ADT, of two or more years.
Survival favoured docetaxel while PFS, SRE, and MFS favoured abiraterone
Patients were stratified and randomised to SOC plus docetaxel at 75 mg/m2 every 3 weeks for 6 courses and prednisone at 5 mg twice daily (n=189), or to SOC plus abiraterone acetate at 1000 mg plus prednisone at 5 mg daily until disease progression (or a maximum of 2 years in non-metastastic patients planned for RT as part of SOC…), n=377. Sixty percent of patients were classified M1 at entry, and 76% had Gleason scores of 8 to 10; the patients’ median age was 66 years and median PSA was 56 ng/ml.
The primary outcome was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors.
The median follow-up was 4 years, at which time 149 deaths had occurred; of these 45 were in the SOC+docetaxel+prednisone arm and 111 occurred in the SOC+abiraterone acetate+prednisone arm. The hazard ratio (HR) for the survival comparison was 1.16 (95% confidence interval [CI] 0.82, 1.65); HR for failure-free survival was 0.51 (95% CI 0.39, 0.67); HR for progression-free survival (PFS) was 0.65 (95% CI 0.48, 0.88); HR for metastatic progression-free survival (MPFS) was 0.77 (95% CI 0.57, 1.03); and HR for symptomatic skeletal events (SSE) was 0.83 (95% CI 0.55, 1.25).
The incidence of grades 3, 4, 5 toxicity, respectively, was 36%, 13%, 1% with SOC+docetaxel+prednisone versus 40%, 7%, 1% with SOC+abiraterone+prednisone.
The choice of treatments at progression was quite different, with many patients exposed then to the other treatment.
The STAMPEDE trial offers a direct, randomised, comparative analysis of two new standards for patients with hormone naive prostate cancer. This comparison was possible only because of the novel platform design of this protocol. Failure–free and progression-free survival clearly favoured SOC+abiraterone+prednisone, and with less certainty, metastasis-free survival favoured SOC+abiraterone+prednisone. However, the design means that abiraterone was given to progression whereas docetaxel was given as short course at start of therapy, meaning docetaxel patients had more salvage options at relapse, including docetaxel rechallenge. This explains the discrepancy between failure and progression-free survival favouring abiraterone but with no ultimate difference seen on overall or cause-specific survival. The proportion of patients having at least one “severe” toxicity was similar between the arms but the type of toxicities was quite different.
These data will help clinicians and patients to choose appropriately where both drugs are available options.
In her discussant talk entitled ‘The Changing Landscape of Prostate Cancer’, Cora Sternberg of the Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy said that adding abiraterone acetate plus prednisolone to ADT is a clinically effective treatment option offering an alternative to docetaxel for men who are starting treatment for the first time. Future research will need to address which of these two agents or whether their combination is most effective, and for whom.
This trial was funded by Cancer Research UK, Medical Research Council, Janssen, Astellas, Clovis Oncology, Novartis, Pfizer, and Sanofi-Aventis.
LBA31_PR – Sydes MR, et al. Adding abiraterone acetate plus prednisolone (AAP) or docetaxel for patients (pts) with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): directly randomised data from STAMPEDE (NCT00268476).