“Final” data on abiraterone acetate in treatment of chemo-naive mCRPC


According to a media release issued on Sunday, the most recent “final” update to the COU-AA-302 trial has shown that treatment with abiraterone + prednisone provided a statistically significant overall survival benefit in the treatment of men with chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC).

Data from this final update to the COU-AA-302 were presented by Charles Ryan, MD, at the ongoing annual meeting of the European Society for Medical Oncology (ESMO) in Madrid, Spain. The media release was issued by Janssen, the manufacturer of abiraterone acetate (Zytiga).

It is important to recognize that this “final update” to the trial results reflects data collected after the formal randomization of the trial had been ended, and that, as a consequence, these data include the results from after that time, when some 44 percent of men in the control arm of the trial, who had initially been tyreated with a placebo + prednisone, were switched to treatment with abiraterone + prednisone.

With that provision, here are the results presented by Ryan in Madrid:

  • The trial originally enrolled 1,088 patients with chemotherapy-naive mCRPC.
  • Average (median) follow-up was 49.2 months.
  • Average (median) overall survival times were
    • 34.7 months for men originally randomized to abiraterone + prednisone
    • 30.3 months for men originally randomized to a placebo + prednisone (whether they subsequently received abiraterone + prednisone or not)
  • The relative reduction in risk of death from initial treatment with abiraterone + prednisone was therefore 19 percent.
  • Average (median) time to use of an opiate to treat cancer-related pain was
    • 33.4 months for men originally randomized to abiraterone + prednisone
    • 23.4 months for men originally randomized to a placebo + prednisone (whether they subsequently received abiraterone + prednisone or not)
  • There was no apparent change in the safety profile of abiraterone acetate after this longer period of follow-up compared to the safety profile from earlier reports.

With the recent approval of enzalutamide (Xtandi) for the treatment of chemotherapy-naive mCRPC here in the USA, we now have four drugs approved for the treatment of men with chemotherapy-naive, metastatic prostate cancer: sipuleucel-T (Provenge), abiraterone acetate (Zytiga), enzalutamide (Xtandi), and radium-223 (Xofigo). Each of these four drugs have now reported a median overall survival benefit (although none of these survival benefits exceed 5 months), and it should be noted that radium-223 is only indicated for the treatment of men who have evident bone-related pain in addition to evident mCRPC status.

8 Responses

  1. LENGTH OF BENEFIT

    Thank you for reporting this update.

    I am especially impressed with the 10 month advantage in time before opiate drugs were needed. Having watched my father struggle with pain and opiods through this period, I find that benefit of great value, especially since the comparison is to men who were switched later to abiraterone.

    ABOUT 3, 4, AND 5 MONTH BENEFITS REPORTED WITH “SUCCESSFUL” DRUGS

    It is so important for patients to be aware that such benefit statistics include all comers, meaning patients who do not respond at all up through the range to the patients who respond spectacularly well. Savvy oncologists will be able to determine whether a patient is responding in around 90 days, as I understand it as a layman, and can switch to another tactic in the arsenal if the patient is a non-responder. Also, this “all-comers” success statistic really implies that responders will typically enjoy much better responses than the median reported. Additionally, such statistics often do not reflect the benefits of combined tactics.

    COMBINING TACTICS

    Renowned prostate cancer researcher and physician Oliver Sartor (Tulane) recently commented that he is frequently using a combination of recently approved drugs for late-stage patients in his practice. His strategy strikes me as similar to the approach that has worked so well for me for my apparently non-metastatic (per sophisticated, advanced scans in 2011/2012), early stage but once life-threatening disease since 1999 — IADT using an LHRH agonist (Lupron for me), an antiandrogen (Casodex, then flutamide in the fourth round for me), and a 5-ARI (Proscar/finasteride, then Avodart from October 2011 to present) plus supporting drugs and lifestyle tactics.

  2. Note — the summary points out that the:

    Average (median) time to use of an opiate to treat cancer-related pain was

    33.4 months for men originally randomized to abiraterone + prednisone
    23.4 months for men originally randomized to a placebo + prednisone

    That’s a 10-month difference. What is not considered is how much cheaper a 10-month supply of morphine is compared to a 10-month supply of abiraterone.

  3. Hi Richard,

    I sense that cost consciousness is rising in our current environment of recently approved drugs that are effective but expensive. Of course in the case you address, actual partial control of the cancer and gaining time for more technology to come into play that might benefit the patient, in addition to pain control by itself, are factors.

    On another note, I recall your interest in estrogen for prostate cancer. I have not pursued that in my own case as a therapy, but I was pleased with transdermal estradiol patches to help preserve bone density during my last round of 18 months of triple ADT. Are you still researching estrogen?

  4. Yes, Jim, I am still studying estrogen in men. I am co-investigator on a major grant to give prostate cancer patients on ADT some add-back estradiol with the goal of reducing the more troubling side effects that we know are due to estrogen suppression.

    If you or others want to see the latest review on “estrogen in men”, please e-mail me directly and I can send you a PDF copy.

    Meanwhile, for all those on ADT, I invite you to check out LIFEonADT.com for info on the ADT book. Also there are now some reviews of the book posted on Amazon.com.

    Richard W.

  5. Hello,

    Zytiga is approved for metastatic castrate resistant prostate cancer. However, I am currently enrolled in a double-blind trial to see if there would be even more benefit if Zytiga was administered immediately at the beginning of the ADT treatment.

    Eligibility rules:
    — Newly diagnosed metastatic prostate cancer (max 3 months)
    — Be at the castrate level (surgical or any ADT drug except … I don’t remember)
    — At least 4 bone metastases (I had 30+)
    — Be in relative good health
    — No metastases to soft tissues

    I am in my eighth month on the trial. From the initial 560, my PSA is currently at 0.30. Still no symptoms, and very minor side effects. I was glad to read that when it works it might work very well. It seems to work in my case whether or not I am receiving Zytiga. The number of the protocol of the study is 212082PCR3011

    PaulP

  6. I am fairly sure that the trial Paul Picard says he is on is this one listed on the ClinicalTrials.gov web site. (The protocol number Paul gives is probably the protocol number assigned by the center where he is being treated.)

  7. Hello,
    I clicked on the link however it does not lead anywhere.

    I live 7.5 hours from where I had to report initially bi-weekly for 3 months then monthly for the next year then every 2 months for the rest of the 2 years.

    I had asked them after a while if they could help in any way just for the extensive travel costs. They declined any kind of help.
    I did not enter this trial hoping for a miracle cure. I just wanted to give some kind of meaning from my cancer situation by making myself available for some gathering of info that might prove useful.

    Because of their attitude I almost withdrew from the research. Why should I care more than they do? Just as an investment point of view, was it a good investment to spend at least $8,000 in travel for only a 50% chance of getting a treatment that is not even proven yet.

    My wife is less Cartesian and she would have killed me if I did quit. Now I agree with her, why change anything to a situation that seems to work super well. Other info … there will be 1270 patients enrolled

    PaulP

  8. Paul: The link now works … and its is the right trial.

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