Loading...
Abiraterone in “high-” and “low-risk” metastatic hormone-sensitive prostate cancer
Hoyle, Alex P Ali, Adnan James, Nicholas D Cook, Adrian Parker, Christopher C de Bono, Johann S Attard, Gerhardt Chowdhury, Simon Cross, William R Dearnaley, David P
Hoyle, Alex P
Ali, Adnan
James, Nicholas D
Cook, Adrian
Parker, Christopher C
de Bono, Johann S
Attard, Gerhardt
Chowdhury, Simon
Cross, William R
Dearnaley, David P
Authors
Hoyle, Alex P
Ali, Adnan
James, Nicholas D
Cook, Adrian
Parker, Christopher C
de Bono, Johann S
Attard, Gerhardt
Chowdhury, Simon
Cross, William R
Dearnaley, David P
Brawley, Christopher D
Gilson, Clare
Ingleby, Fiona
Gillessen, Silke
Aebersold, Daniel M
Jones, Rob J
Matheson, David
Millman, Robin
Mason, Malcolm D
Ritchie, Alastair WS
Russell, Martin
Douis, Hassan
Parmar, Mahesh KB
Sydes, Matthew R
Clarke, Noel W
Ali, Adnan
James, Nicholas D
Cook, Adrian
Parker, Christopher C
de Bono, Johann S
Attard, Gerhardt
Chowdhury, Simon
Cross, William R
Dearnaley, David P
Brawley, Christopher D
Gilson, Clare
Ingleby, Fiona
Gillessen, Silke
Aebersold, Daniel M
Jones, Rob J
Matheson, David
Millman, Robin
Mason, Malcolm D
Ritchie, Alastair WS
Russell, Martin
Douis, Hassan
Parmar, Mahesh KB
Sydes, Matthew R
Clarke, Noel W
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2019-08-23
Submitted date
Alternative
Abstract
Background Abiraterone 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). Objective Evaluation of heterogeneity of effect between LATITUDE high- and low-risk M1 prostate cancer patients receiving ADT + AAP in the STAMPEDE trial. Design, setting, and participants A 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 analysis The 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 limitations A 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. Conclusions Men with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for “risk” or “volume”. Patient summary Coadministration 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.
Citation
Hoyle, A. P. et al. (2019) Abiraterone in “high-” and “low-risk” metastatic hormone-sensitive prostate cancer, European Urology, 76(6), pp.719-728 https://doi.org/10.1016/j.eururo.2019.08.006
Publisher
Journal
Research Unit
PubMed ID
PubMed Central ID
Embedded videos
Type
Journal article
Language
en
Description
This is an accepted manuscript of an article published by Elsevier in European Urology on 23/08/2019, available online: https://www.sciencedirect.com/science/article/abs/pii/S0302283819306207?via%3Dihub
The accepted version of the publication may differ from the final published version.
Series/Report no.
ISSN
0302-2838
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
This study was supported by Cancer Research U.K., Medical Research Council, Astellas Pharma, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi Aventis.