Abiraterone and Increased Survival in Metastatic Prostate Cancer
- Study type
- Clinical trial
- Study name
- COU-AA-301
- Phase
- Phase 3
- Design
- Randomised, placebo-controlled trial (2:1 randomisation)
- Sample size
- 1195 patients
- Source
- N Engl J Med · 2011
- Trial registration
- NCT00638690
In plain words
In this study, men with advanced prostate cancer that had kept growing despite docetaxel chemotherapy were given either the drug abiraterone with prednisone or a placebo (dummy drug) with prednisone. Patients who took abiraterone typically lived longer (14.8 months versus 10.9 months). Side effects such as swelling and fluid retention, high blood pressure and low blood potassium were more common in the abiraterone group.
Key results
Treatment arms and regimens
Abiraterone acetate 1000 mg (4 × 250 mg tablets) orally once daily, at least 1 hour before and 2 hours after a meal, with prednisone or prednisolone 5 mg orally twice daily, until disease progression (797 patients).
Placebo (4 tablets once daily) with prednisone or prednisolone 5 mg twice daily (398 patients).
Source of the regimen details: Full text of the paper (PMC3471149) and ClinicalTrials.gov NCT00638690
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
1195 patients with metastatic castration-resistant prostate cancer who had previously received docetaxel (up to two previous chemotherapy regimens), with PSA progression or radiographic progression, ECOG performance status 0 to 2 and continued castration. Patients with AST/ALT ≥2.5 times the upper limit of normal (or >5 times with liver metastases) were excluded.
Endpoints
Primary endpoint: overall survival. Secondary endpoints: time to PSA progression (PSA rise according to prespecified criteria), radiographic progression-free survival according to prespecified criteria, and PSA response rate.
Safety and side effects
Mineralocorticoid-related adverse events (fluid retention and oedema, hypokalaemia, hypertension), cardiac disorders and liver function test abnormalities were more common with abiraterone (55% versus 43%; P<0.001). Grade 3–4 hypokalaemia (laboratory): 5.3% versus 1.0%. Grade 3–4 liver function test abnormalities 3.5% versus 3.0%. Discontinuation because of adverse events 19% versus 23%. After one case of grade 4 aminotransferase elevation, liver test monitoring was increased during the first 12 weeks.
Clinical significance and place in guidelines
This study showed that inhibiting androgen biosynthesis with abiraterone acetate prolongs overall survival in patients with metastatic castration-resistant prostate cancer who have previously received chemotherapy. The drug's current place in guidelines and its approval status should be checked against up-to-date sources, as the abstract does not address these.
Limitations
The data were unblinded at the interim analysis because the results had exceeded the preplanned criteria for stopping the study; median follow-up was 12.8 months. The study population was limited to patients who had previously received docetaxel. The study was funded by Cougar Biotechnology.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.