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; Brawley, Christopher D; Gilson, Clare; Ingleby, Fiona; Gillessen, Silke; Aebersold, Daniel; Jones, Rob J; Matheson, David; Millman, Robin; Mason, Malcolm D; Ritchie, Alastair W S; ... (2019). Abiraterone in "High-" and "Low-risk" Metastatic Hormone-sensitive Prostate Cancer. European urology, 76(6), pp. 719-728. Elsevier 10.1016/j.eururo.2019.08.006

Text 1-s2.0-S0302283819306207-main.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (2MB)

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.

Interest & Impact

Downloads

3 since deposited on 04 Sep 2019
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item