Response to enzalutamide as third-line treatment for mCRPC

According to a new article in Cancer, treatment with enzalutamide for men with metastatic, castration-resistant prostate cancer (mCRPC) after prior treatment with both docetaxel-based chemotherapy and abiraterone acetate demonstrated “modest” clinical activity.

Badrising et al. (a Dutch clinical research group) report a retrospective analysis of data from a series of 61 patients. Here are the details from their study:

  • All patients had progressive mCRPC and were treated with docetaxel-based chemotherapy and with abiraterone acetate prior to treatment with enzalutamide.
  • Average (median) age of participants was 69 years.
  • 57/61 patients (93 percent) had an ECOG performance status of between 0 and 2.
  • Patients’ metastatic status was as follows:
    • 48/61 men (79 percent) had metastasis to bone.
    • 13/61 men (21 percent) had visceral (soft tissue) metastases.
    • 33/61 men (54 percent) had lymph node metastases.
  • Median duration of treatment with enzalutamide was 14.9 weeks.
  • 13/61 patients (21 percent) had a PSA decline of  ≥ 50 percent.
  • Median time to biochemical (PSA-based) progression was 17.4 weeks.
  • Median time to progression-free survival was 12.0 weeks.
  • Median time to overall survival was 31.6 weeks.
  • Prior PSA responses to treatment with docetaxel-based chemotherapy or with abiraterone acetate did not appear to predict PSA response to enzalutamide.
  • The most frequent, significant adverse reactions to treatment with enzalutamide (Grade 2 and higher) were fatigue and musculoskeletal pain.

It would appear from this paper that, as might have been expected, a subset of men who have received prior treatment with docetaxel-based chemotherapy and abiraterone acetate can still have a really meaningful response to enzalutamide (the 21 percent of men in this study whose PSA declined by ≥ 50 percent) but many men who receive enzalutamide as a third-line treatment for mCRPC will not have such a meaningful response. One might expect to see a similar type of response to abiraterone acetate if this agent was used as the third-line therapy (after chemotherapy and enzalutamide).

10 Responses

  1. My PSA continued to rise during treatment with docetaxel, abiraterone, and enzalutamide. It is now 1,400, up from 28 ng/ml when I started chemo.

    Wonder drugs may work for a few but certainly not the majority. It leaves you wondering if they are worth all that money.

  2. Dear David:

    There is absolutely no doubt at all that we need ways to be able to project, up front, which patients are most likely to respond well to many of the new drugs that are already available or are currently in development. No one in his (or her) right mind wants to have to take — or to pay for — a drug that has no clinical benefit. There is ongoing research in this area … but no good answers at this time.

  3. The overall median survival of 31.6 weeks seems modest as well.

    As this article mentions, patients had mCRPC and were previously treated with docetaxel and with abiraterone. It would be interesting to know if any of them — after enzalutamide failure — also received other treatments that prolong survival, such as cabazitaxel. If not, what impact would it have on survival? … We can only guess … or wait for further studies.

    By the way this recently published study also showed a “modest response” for a smaller but apparently very similar group of patients.

  4. Dear Pawel,

    In answer to your question, after docetaxel, abiriterone, and then enzalutamide (none of which seemed to do any good), I moved on to EcarboF ,which made my PSA rocket up even more, and scans showed faster growth of metastasis, including into bones for the first time.

    I am now on cabazitaxel (just completed two rounds, with next one tomorrow), and, miracle of miracles, my PSA has dropped to below 1,000 for first time in a year.

    Maybe that is what I needed all along? I’ll let you know (if I am around!) what my survival time is. By the way, curiously, I feel fine, have a good appetite and am pretty active.


  5. Pawel (and David too):

    David’s case history provides a classic example of the core problem associated with current treatment of advanced forms of prostate cancer … how to actually be able to identify the best therapy for a specific patient with a specific subtype of prostate cancer at a specific point in the course of his disease so as to (a) avoid wasting time with therapies that aren’t going to be effective (or, necessarily, safe) and (b) get the patient onto the best possible treatment as soon as possible.

    Frankly, we really don’t know how to do this yet … but there is evolving research in this area, and I am optimistic that there will be real progress in the near future. Whether that “near future” is a year away or 10 years away is a much harder question to answer of course! In the meantime (David), I hope you continue to do really well on the cabazitaxel. Some men clearly do.


    Both the article and David’s experience impress me that we now have an arsenal of drugs each of which is often effective for a substantial proportion of patients. It used to be just docetaxel with prednisone. But these days, in early 2014, if one drug does not work, or after it or a combination have stopped working, there are more drugs to try, with additional drug candidates well along in the pipeline. We also have better monitoring techniques, such as the Na18F PET/CT bone scan and for lymph nodes the emerging feraheme USPIO scan and calcium isotope scans; these should help us identify successful drugs for each of us earlier than with older methods.

    David, I hope you gain enough time that a drug that is a breakthrough for you will come to the rescue. Hang in there!

  7. Thanks Jim.

    I have started asking about Xofigo as a treatment for the metastases in my bones, but it appears that is not yet available. My consultant told me on Friday that he hoped to be able to get his hands on some of it soon, however.

    I share your view that there always seems to be something new coming down the pike to keep me going. I do feel a bit of a fraud, feeling so well, after 13 years of prostate cancer, and now that my PSA has dropped to below 1,000, thanks to the cabazitaxel, I am starting to think in terms of another 13 years.

  8. Dear David:

    It appears that NICE will be issuing draft guidance on the use of radium-223 (Xofigo) in the UK very soon (i.e., February). Click here to see the details. Of course a lot is going to depend on the willingness of the manufacturer to agree to what NICE sees as an affordable price.

  9. I seem to be very lucky at getting all these wonder treatments out of the drug companies! I am not sure what I have done to deserve it, but my NHS consultants are obviously very persuasive.


  10. Good for them! … Which is obviously good for you too … even if they don’t all work as well as one would like!

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