Can galeterone show effectiveness in men with AR-V7 mCRPC?

According to a report in The ASCO Post last night, the investigational drug galeterone may have significant clinical activity against a specific subtype of castration-resistant prostate cancer (CRPC) known as AR-V7.

Data supporting this finding have just been presented by Mary-Ellen Taplin and colleagues at the ongoing EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, and are reviewed in detail in this report on The ASCO Post web site.

According to Dr. Taplin:

In a subset of seven patients who had circulating tumor cells with a higher ratio of N-terminal compared to C-terminal androgen receptors and so were likely to have the AR-V7 variant, six had favorable PSA responses to galeterone.

If these preliminary findings can be confirmed, it would be important for men who carry the AR-V7 subtype of CRPC and who therefore do not respond well to treatment with either abiraterone acetate or enzalutamide (as previously reported based on studies by Antonarakis et al.).

According to the report on The ASCO Post web site, and based on data from the ARMOR 2 trial of galeterone in men with CRPC:

  • Data from 60 patients who had not received prior treatment with either abiraterone or enzalutamide were available for evaluation.
    • PSA levels declined by ≥ 30 percent in 50/60 (83 percent) of these patients.
    • PSA levels went on to decline by ≥ 50 percent in 42/60 (70 percent) of these patients.
  • Data from 37 patients who were resistant to abiraterone acetate were available for evaluation.
    • PSA levels declined by any amount in 13/37 (35 percent) of these patients.
  • Data from 9 patients who were resistant to enzalutamide were available for evaluation.
    • PSA levels declined by any amount in 5/9 (56 percent) of these patients.
  • Circulating tumor cells (CTC levels) were evaluated in 71 patients and were more elevated in 64 patients (90 percent) who had more advanced forms of cancer that had failed a higher number of earlier treatments.

Apparently Tokai Pharmaceuticals now intends to conduct a randomized Phase III clinical trial of galeterone vs. enzalutamide in the treatment of men with metastatic CRPC who carry the AR-V7 variant. In other words, patients with metastatic or non-metastatic CRPC will be randomized to treatment with either galeterone or enzalutamide alone.

While this would be the first Phase III trial of any drug for the treatment of prostate cancer in a specific subset of men carrying a particular biomarker (the AR-V7 variant in CTCs), it should also be noted that this biomarker is relatively uncommon and so enrollment of men into this trial might be challenging. As yet it is unclear how many men might need to be enrolled into such a Phase III trial to show a clinically significant difference in outcomes between the two forms of treatment. It is also unclear exactly what the appropriate primary endpoint for such a trial might be.

One Response

  1. Great that this is progressing to a Phase III trial. Unfortunately, for men who have already failed abiraterone and enzalutamide, this trial does not give them an opportunity to participate. Personally I’d like to see a trial with galeterone and Taxotere. Given the potential AR-V7 resistance of Taxotere, that might be more meaningful.

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