Does abiraterone acetate resistance induce cross-resistance to docetaxel-based chemotherapy?

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.

4 Responses

  1. It is difficult to draw any conclusions based on such a small number of patients, but the resistance induced by Zytiga is of concern. (There have already been several posts [elsewhere] on this subject in which people were considering whether a combination of enzalutamide and Zytiga could be used to avoid this phenomenon.) The future will bring the answer. …

  2. I agree with Jean. It is very difficult to draw any conclusion. I came across many posts regarding prostate cancer. I would like to share one that I found interesting.

    [Editoral note: The link above is only accessible if you are a member of a specific web site referred to. Most readers of The “New” Prostate Cancer InfoLink are probably not going to be able to link to that site.]

  3. My conclusion from this study was that there was not cross resistance between abiraterone and docetaxel, and that 26% of men relapsed on abiraterone reponded to docetaxel. Mechanistically these two agents have very different resistance pathways and so cross resistance is unlikely.

  4. The data shows there was a much higher response to docetaxel treatment than I had originally thought. The 26% response rate refers to men having a PSA decline of at least 50%. There were a further 37% who achieved a greater than 30% decrease in PSA. Getting any PSA decrease in a drug-resistant scenario is impressive and taken together shows there was a 63% response to docetaxel post abiraterone.

    The authors of this paper have started with a premise that abiraterone induces cross-resistance to docetaxel and have displayed the data to try and support this. However their catagorisation of the 8 patients who did not respond to docetaxel as “abiraterone resistant” is nonsense and these should be characterised as “abiraterone and docetaxel resistant”. All the patients in this study should already be classified as “abiraterone resistant” since they had relapsed on this drug.

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