Abiraterone in Metastatic Hormone-Sensitive Prostate Cancer

[Balsam01]

TAKE-HOME MESSAGE

•This is a post-hoc analysis of the STAMPEDE study, where the outcomes of metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation (ADT) or ADT + abiraterone acetate were compared by risk according to LATITUDE criteria (≥3 metastases on bone scan; Gleason >7; visceral metastases). A total of 428 patients (48%) had low-risk disease. Patients receiving ADT + abiraterone acetate had improved overall survival (HR, 0.66) and failure-free survival (HR, 0.24) compared with ADT alone. No difference in effect was observed between low- and high-risk groups for overall survival or failure-free survival.

•These data support treatment intensification with abiraterone acetate for all men with metastatic disease, independent of risk.

– Pedro C. Barata, MD

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.

European Association of Urology

Abiraterone in "High-" and "Low-Risk" Metastatic Hormone-Sensitive Prostate Cancer

Eur Urol 2019 Aug 22;[EPub Ahead of Print], AP Hoyle, A Ali, ND James, A Cook, CC Parker, JS de Bono, G Attard, S Chowdhury, WR Cross, DP Dearnaley, CD Brawley, C Gilson, F Ingleby, S Gillessen, DM Aebersold, RJ Jones, D Matheson, R Millman, MD Mason, AWS Ritchie, M Russell, H Douis, MKB Parmar, MR Sydes, NW Clarke

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[tom67inMA]

WOW!!! "failure-free survival (HR, 0.24) compared with ADT alone". I read so many studies that show advantages to some drug or treatment, but the HR is only 0.85. What really impresses me with early Abiraterone isn't the 5 year survival advantage, but rather the number of 5 year survivors for which Abiraterone is still working.

[Schwah in reply to tom67inMA]

I don’t want to sound stupid but I always get confused. What exactly does the old .24 number mean?

[tom67inMA in reply to Schwah]

Good question actually. Let me explain my understanding, and others can correct me if I'm wrong: let's assume there were 100 men in the ADT group, and 80 of them progressed in 5 years, so 80% the reference point for 1.00.

For simplicity, let's assume 100 men in the experimental group, but only 20 of them progressed. 20/80 = 0.25 hazard ratio. If all of them progressed, the ratio would be 100/80 = 1.25, and the drug would be a failure.

Based on this understanding, the time frame of the study is very important. If you were to run it for a month, there wouldn't be enough deaths or progression to make a meaningful difference. In a 50 year prostate cancer study, most subjects would be over 100 by the end, and again, no difference. This becomes very important when talking about using PSA testing as a screening tool, because it's best at detecting cancers that won't kill you in 5 years, but may kill in 10 or 20.

[Schwah in reply to tom67inMA]

Thx. Very good explanation

[TommyTV]

Interesting, but I already knew this from personal experience. I’m at 8 years after a dx PSA of 571, multiple Mets, stage4. I was asked to join STAMPEDE trial in U.K. PSA is still immeasurable.