• Alex P Hoyle, Adnan Ali, Nicholas D James, Adrian Cook, Christopher C Parker, Johann S de Bono, Gerhardt Attard, Simon Chowdhury, William R Cross, David P Dearnaley, Christopher D Brawley, Clare Gilson, Fiona Ingleby, Silke Gillessen, Daniel M Aebersold, Rob J Jones, David Matheson, Robin Millman, Malcolm D Mason, RitchieAlastair W SAWSRoyal Marsden Hospital, Sutton, UK., Martin Russell, Hassan Douis, ParmarMahesh K BMKBMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK., Matthew R Sydes, Noel W Clarke, and STAMPEDE Investigators.
• The Christie and Royal Salford Hospitals, Manchester, UK; Genito Urinary Cancer Research Group and the FASTMAN Centre of Excellence, Division of Cancer Sciences, The University of Manchester, Manchester, UK.
• Eur. Urol. 2019 Dec 1; 76 (6): 719-728.

BackgroundAbiraterone acetate received licencing for use in only "high-risk" metastatic hormone-naïve prostate cancer (mHNPC) following the LATITUDE trial findings. However, a "risk"-related effect was not seen in the STAMPEDE trial. There remains uncertainty as to whether men with LATITUDE "low-risk" M1 disease benefit from androgen deprivation therapy (ADT) combined with abiraterone acetate and prednisolone (AAP).ObjectiveEvaluation of heterogeneity of effect between LATITUDE high- and low-risk M1 prostate cancer patients receiving ADT + AAP in the STAMPEDE trial.Design, Setting, And ParticipantsA post hoc subgroup analysis of the 2017 STAMPEDE "abiraterone comparison". Staging scans for M1 patients contemporaneously randomised to ADT or ADT + AAP within the STAMPEDE trial were evaluated centrally and blind to treatment assignment. Stratification was by risk according to the criteria set out in the LATITUDE trial. Exploratory subgroup stratification incorporated the CHAARTED criteria.Outcome Measurements And Statistical AnalysisThe primary outcome measure was overall survival (OS) and the secondary outcome measure was failure-free survival (FFS). Further exploratory analysis evaluated clinical skeletal-related events, progression-free survival (PFS), and prostate cancer-specific death. Standard Cox-regression and Kaplan-Meier survival estimates were employed for analysis.Results And LimitationsA total of 901 M1 STAMPEDE patients were evaluated after exclusions. Of the patients, 428 (48%) were identified as having a low risk and 473 (52%) a high risk. Patients receiving ADT + AAP had significantly improved OS (low-risk hazard ratio [HR]: 0.66, 95% confidence interval or CI [0.44-0.98]) and FFS (low-risk HR: 0.24, 95% CI [0.17-0.33]) compared with ADT alone. Heterogeneity of effect was not seen between low- and high-risk groups for OS or FFS. For OS benefit in low risk, the number needed to treat was four times greater than that for high risk. However, this was not observed for the other measured endpoints.ConclusionsMen with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for "risk" or "volume".Patient SummaryCoadministration of abiraterone acetate and prednisolone with androgen deprivation therapy (ADT) is associated with prolonged overall survival and disease control, compared with ADT alone, in all men with metastatic disease starting hormone therapy for the first time.Copyright © 2019. Published by Elsevier B.V.

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