A paper in the Annals of Oncology suggests that treatment with abiraterone acetate may induce a loss of effectiveness of docetaxel-based chemotherapy and that men with metastatic, castration resistant prostate cancer (mCRPC) who do not respond to abiraterone acetate will also not respond to docetaxel-based chemotherapy.
Mezynski et al. carried out a retrospective analysis of data from 54 patients with mCRPC who were also treated with abiraterone acetate. Of these 54 patients, 35 were subsequently treated with docetaxel-based chemotherapy.
Here is what the authors have reported:
- PSA decreases among docetaxel-treated patients were
- ≥ 50 percent in 9/35 patients (26 percent), with a median time to PSA progression of 4.6 months
- ≥ 30 percent in another13/35 patients (37 percent)
- 0 in 8/35 patients (23 percent)
- The average (median) overall survival was 12.5 months.
- The 8/35 patients who failed to achieve any PSA decrease on abiraterone acetate were defined as abiraterone-refractory.
- All 8 abiraterone-refractory patients were also docetaxel-refractory.
- Partial reponses to docetaxel were observed in 4/24 patients with radiologically evaluable disease (11 percent).
- None of these 4 men were abiraterone-refractory.
The authors conclude that:
- The activity of docetaxel given after abiraterone appears to be lower than anticipated.
- Abiraterone-refractory patients appear to be non-responsive to docetaxel-based chemotherapy.
Whether this is a good reason to not treat men with abiraterone acetate prior to docetaxel is not answerable at this time. However, it does raise the interesting question of whether, once enzalutamide is available, a better therapeutic strategy may be to treat men with mCRPC first with enzalutamide, then with docetaxel-based chemotherapy, and only then with abiraterone acetate. However, such questions will need to be addressed in well-designed clinical trials over time.