Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol

Abstract

BackgroundAdding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP.MethodRecruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP.ResultsA total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8–10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82–1.65); failure-free survival HR = 0.51 (95% CI 0.39–0.67); progression-free survival HR = 0.65 (95% CI 0.48–0.88); metastasis-free survival HR = 0.77 (95% CI 0.57–1.03); prostate cancer-specific survival HR = 1.02 (0.70–1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55–1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm.ConclusionsThis direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.Trial registrationClinicaltrials.gov: NCT00268476.

Clinical effectiveness of docetaxel for castration‐sensitive prostate cancer in a real‐world population‐based analysis

“…Other treatments may also become viable options after the completion of randomized phase 3 trials, such as enzalutamide (NCT02446405) or apalutamide (NCT02489318). The STAMPEDE study provides some comparison between abiraterone and docetaxel in this setting . The STAMPEDE trial was designed to compare different intervention arms to standard of care (ADT alone at the time).…”

“…More recently, the use of abiraterone acetate and prednisone with ADT in the early castration‐sensitive setting was also shown to improve overall survival in the LATITUDE and STAMPEDE (Arm G) phase III clinical trials. There have been no prospective clinical trials comparing docetaxel and abiraterone in this setting, although some analyses show similar efficacy . However, this does not take into account challenges encountered when delivering chemotherapy in a real‐world setting.…”

Management of advanced prostate cancer in a middle‐income country: real‐world consideration of the Advanced Prostate Cancer Consensus Conference 2017

“…This was confirmed by the STAMPEDE study showing that ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone among men with locally advanced or metastatic prostate cancer . Comparative analysis of chemohormonal therapy vs ADT plus abiraterone and prednisolone from the STAMPEDE study showed comparable OS and prostate cancer‐specific survival .…”

The Management of Patients with Metastatic Prostate Cancer during the COVID-19 Pandemic

“…The STAMPEDE trial also compared abiraterone acetate and docetaxel in patients with mHSPC and showed no evidence of a difference in overall or prostate cancer-specific survival, or other important outcomes such as symptomatic skeletal events. The worst toxicity grade was similar but comprised different toxicities in line with the known properties of the drugs [34].…”