New test for abiraterone- and enzalutamide-resistant forms of prostate cancer

A group at The Institute for Cancer Research and The Royal Marsden Hospital in the UK — along with other European colleagues — has come up with a new, relatively low-cost test that seems to be able to identify men with advanced forms of prostate cancer who are more or less likely to respond well to treatment with drugs like abirateone acetate and enzalutamide.

Detailed information about this new test can be found in the article by Conteduca et al. in Annals of Oncology, and also in commentary on the ScienceDaily web site.

Basically, the new test can be used to assess androgen receptor gene status based on blood samples. It has been tested to date in men with castration-resistant prostate cancer (CRPC), and the research team has been able to show the following:

  • In an initial patient cohort, so-called “AR gain” (which means the number of copies of the androgen receptor gene and mutations to that gene) was found in 14 percent of chemotherapy-naïve patients and 34 percent of post-docetaxel patients.
  • Compared to the men with no “AR gain”, the patients in this cohort with “AR gain” had
    • Worse overall survival among the chemotherapy-naïve patients (hazard ratio (HR) = 3.98; P <0.001)
    • Worse overall survival among the post-docetaxel patients (HR = 3.81; P <0.001)
    • Worse progression-free survival among the chemotherapy-naïve patients (HR = 2.18; P =0.03)
    • Worse progression-free survival among the post-docetaxel patients (HR = 1.95; P =0.01), respectively)
    • A lower rate of PSA decline to ≥ 50 percent of its original level among the chemotherapy-naïve patients (odds ratio [OR] = 4.7; P =0.035)
    • A lower rate of PSA decline to ≥ 50 percent of its original level among the post-docetaxel patients (OR = 5.0; P =0.003), respectively].
  • Important AR mutations
    • Were observed in 11 percent of post-docetaxel patients
    • Were not observed in any chemotherapy-naïve, abiraterone-treated patients
    • Were again also associated with worse overall survival (HR = 3.26; P =0.004).
  • Data from a second group of patients confirmed the initial data above.
  • Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts.

Apparently this test is going to be assessed in prospective clinical trials in the near future and could become an important method for determining which patients with CRPC are good candidates for treatment with drugs like abiraterone and enzalutamide as opposed to which patients are not good candidates for treatment with these types of therapy.


4 Responses

  1. So if you are not a good candidate for these two drugs, what are the alternatives if any?

  2. Very interesting post, thank you for the summary.

    Quick question: The authors write that pre-chemo use of Zytiga was not associated with the emergence of important AR mutations. They don’t say the same for Xtandi in the pre-chemo setting.

    Does this imply (given the limits of this small study) that pre-chemo Zytiga use suppresses, or at least delays, the formation of AR gene mutations? That would be a significant insight at this treatment stage.

    Thanks again!

  3. Herschell:

    If you aren’t a good candidate for either of these two drugs after standard forms of androgen deprivation therapy (ADT, also known as hormone therapy), there are really only three options at this time:

    — Chemotherapy, with either docetaxel/Taxotere or cabazitaxel/ Jevtana
    — A completely different form of hormonal therapy, using estrogen patch therapy
    — A clinical trial of one of the investigational drugs in development

    A lot would depend on your individual disease characteristics and other health factors that may be relevant, and you would be wise to get the opinion of a specialized medical oncologist who treats a lot of prostate cancer patients (if you haven’t already seen one).

  4. Dear Ifri:

    I don’t think we really have a good answer to that question as yet … and my suspicion is that it would probably depend on the precise genetic/genomic make-up of the individual cancer in the individual patient. Things get very complicated at this stage of managing progressive prostate cancers.

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