An update on development of abiraterone acetate


On Tuesday this week, three papers about abiraterone acetate were published in the on-line version of the Journal of Clinical Oncology. These articles are reports of data previously presented at various clinical/scientific meetings, but at least they are now available in a peer-reviewed journal.

In the first of the three papers, Reid et al. report on the antitumor activity of abiraterone in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). This was a two-stage, Phase I/II study, and the first stage was met so we will only give the results of the full Phase II study. All patients were treated with 1,000 mg abiraterone acetate, once a day, and the study showed the following:

  • 47 docetaxel-treated patients with CRPC were enrolled.
  • PSA declines of 30 percent or higher were observed in 32/47 patients (68 percent).
  • PSA declines of 50 percent or higher were observed in 24/47 patients (51 percent).
  • PSA declines of 90 percent or higher were observed in 7/47 patients (15 percent) of patients.
  • Partial responses (by RECIST criteria) were reported in 8/30 patients with measurable disease (27 percent).
  • The median time to PSA progression was 169 days.
  • The median number of weeks on study was 24.
  • 12/47 patients (25.5 percent) remained on study for 48 weeks.
  • The levels of circulating T cells (CTCs) were assessed in 34 patients, of whom 27/34 (79 percent) had ≥ 5 CTCs at baseline; 11/27 patients (41 percent) had a decline from ≥ 5 to < 5 CTCs and 18/27 patients (67 percent) had a 30 percent decline in CTCs after starting treatment with abiraterone acetate.

In the second paper, Danila et al. report data from a trial designed to evaluate the efficacy and safety of abiraterone acetate in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with abiraterone monotherapy.

In this study, 58 men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received abiraterone (1,000 mg once daily) with prednisone (5 mg twice daily). Nearly half of these patients (27/58 or 47 percent) had received prior ketoconazole.

The results of this study showed that:

  • A decline in PSA level of ≥ 50 percent or higher was confirmed in 22/58 patients (36 percent), including 14/31 patients (45 percent) who were ketoconazole-naïve and 7/27 patients (26 percent) who were ketoconazole-pretreated.
  • Partial responses were seen in 4/22 patients (18 percent) with RECIST-evaluable target lesions.
  • Improved ECOG performance scores were noted in 28 percent of patients.
  • The median time to PSA progression was 169 days.
  • CTC conversions with treatment from ≥ 5 to < 5 were noted in 10/29 patients (34 percent).

Taken together, the data from these two trials show that abiraterone + predisone had significant activity in heavily pretreated patients and that abiraterone alone has significant activity in docetaxel-treated patients with CRPC. The side effects associated with abiraterone acetate continue to be relatively minor, but the incidence of hypertension or hypokalemia in docetaxel-pretreated patients was reduced by adding low-dose prednisone to abiraterone acetate.

The third paper, by Ryan et al. provides additional information from a Phase I trial of abiraterone treatment in men who had all had ketoconazole therapy prior to treatment with abiraterone acetate.

Two randomized, double-blind, multicenter Phase III clinical trials of abiraterone acetate are now ongoing. In the first of these trials, abiraterone + prednisone is being tested against a placebo + prednisone in patients with progressive CRPC after treatment with docetaxel chemotherapy. This trial is fully enrolled, and we can reasonably expect the primary outcome of this trial by some time in late 2011. In the second Phase III trial, abiraterone + prednisone is being tested against a placebo + prednisone in CRPC patients before they receive chemotherapy. This trial is not yet fully enrolled, and we have heard that it may be taking longer to accrue patients to this trial than it did to the first abiraterone trial. It is hard to project when the results of this trial might be announced.

14 Responses

  1. Dear Madame or Sir:

    I am writing to you today in desperation for help for my father who is suffering terribly from end-stage prostate cancer. I am trying to petition anyone who would be able to get him the abiraterone drug and I believe this would help him.

    At this point, he does not quality for any study but in order to save his life, I am asking for help to get him this therapy in some way.

    My father means the world to me and I would be forever indebted to you for your help.

    I will anxiously await your reply. Please help us to save his life.

    With sincere gratefulness,

    Lorraine Franzi

  2. Dear Lorraine:

    I am very sorry to hear about your father’s situation, but far as I am aware, the only people who could possibly make the decision to provide abiraterone for treatment of your father is the owner of the drug — now Ortho Biotech Oncology Research & Development (a division of Johnson & Johnson). If they have a compassionate use protocol in place, then it may be possible for your father to receive abiraterone through that protocol. Their chief medical officer is Arturo Molina, MD.

    However, I would point out that there are several other drugs in development that may also be helpful for your father — and they may be even better than abiraterone. I would suggest that you click here to see the article earlier today dealing with all of the drugs currently in later stage development for advanced prostate cancer.

  3. Could you please let me know when this drug is expected to come out? … My father has this prostate cancer and I am trying everything to help him … Thanks so much!

  4. Dear Kathy:

    If the data from the first of the two Phase III clinical trials for abiraterone acetate show a clear survival benefit, I think that it might be approved in the USA some time before July 2011. It might be earlier depending on how good the data are.

    In the meantime, you might like to have a look at this article, which will give you more information about sebveral other drugs in development. Your Dad may be eligible for one or more of these clinical trials.

    You should also be aware that cabazitaxel (Jevtana) was approved by the FDA just a few weeks ago.

  5. Dear Lorraine:

    First I need to apologize for my English. But I write you from Germany.

    I read your comment a few days ago and that’s exactly how I feel. My dad has prostate cancer. They tried so many therapies but without a positive result.
    We met another man who was one of the German patients in the clinical trial for abiraterone. The history of this man and the process of his disease sounds like a twin of my father. The abiraterone took a very positive effect. So he have good hopes that it would help my father as well. But here in Germany, we don’t get so much information about the abiraterone and when it will come out.

    I’m so scared about losing my dad, because he means the world to me. There is no day without tears and sadness. I don’t want to lose him; we don’t want to lose him. We wan to rescue his life, and I would do everything to help him.

    Maybe you have some new information and you have already contacted the medical officer. If so, I would be so grateful to get an answer from you. Click here to send me an e-mail.

    Anyway I wish you, your father and your family the strength to fight the cancer and to rescue his life. It’s not easy to keep the hope, but we need to keep it.

    Kind Regards

    Conny

  6. Conny (and others):

    As far as I know, all the Phase III trials of abiraterone acetate are fully enrolled, and the drug is not likely to be available unless the results of the first trial (in patients who have already received chemotherapy) are positive, in which case it might become available (at least in America) late this year or some time early next year.

    However, there are several other drugs that are in Phase III that patients may be eligible for. We strongly suggest that you look at the information on this commentary, published just after the annual meeting of ASCO.

  7. Hello. I wonder if you can help, my father has stage 4 advanced prostate cancer that has metasised to the bones and lymph glands. He is now in some pain in his leg and back.

    Initially he was given Zoladex, which was effective for 16 months; he then had to go on Casodex, which was not effective, and the doctor advised they wanted to start chemotherapy. However, the blood count was too low after having a blood transfusion and so they have given him stilboestrol and bisphosphonates and a course of steroids.

    We are actively seeking abiraterone and cabazitaxel. Is there any further advance on the release of these drugs in England, USA or any other country?
    Your advice in this matter would be really appreciated as we are at the end of our tether and extremely worried.

    Many thanks.

    Andy, his son

  8. Dear Andy:

    First, if your Dad wasn’t able to have standard chemotherapy (using a docetaxel-based regimen) then cabazitaxel is going to be a very risky form of treatment because it is associated with more serious side effects than docetaxel.

    Second, abiraterone is available at a few centers in the USA on a compassionate use basis — but only for men who have already been treated with a taxane-based form of chemotherapy, so I don’t think your Dad will be eligible. Sorry.

    However, there are other options. Your Dad may be eligible for this clinical trial of MDV3100 (a drug with similar effects to abiraterone). The trial is for men like your Dad who have metastatic disease but have never received chemotherapy. There is no trial site listed in the UK yet, but if you contact the drug company Astellas Pharma in the UK, they may be able to tell you whether trial sites are going to be opening in the UK soon.

    Your Dad may also be eligible for this clinical trial of orteronel (also known as TAK-700; another abiraterone-like drug that is in development) in men with chemotherapy-naive castration-resistant prostate cancer. The trial has only just started, so no trial site is listed in the UK as yet, but I expect there will be trial sites opening in the UK soon. In this case, try contacting the UK Research & Development labs for Takeda Pharmaceuticals.

    The other place that would be worth contacting is the laboratory of Dr. Johann de Bono at the Drug Development Unit at the Royal Marsden Hospital in Sutton in Surrey. That center is involved in much of the rapid evolutionary research on new drugs for the treatment of late stage prostate cancer. If there are other ways to get hold of appropriate development stage drugs that might help your Dad in the UK, they will probably know about them.

  9. Thank you so much for your advice. I really appreciate it and will contact the places you recommended. One other point I did not mention: my father has had one dose of radiotherapy. Will that affect his eligibility for the trials?

    Many thanks

    Andy

  10. Dear Andy:

    I do not believe that a single dose of radiation would affect eligibility for these trials, but only one of the trial centers could actually confirm that for you.

  11. Hola, mi padre empieza hoy con el tratamiento de abiraterone, nos ha costado mucho, al final he podido contactar con JANSSEN y lo hemos pedido por uso compasivo a partir de un hospital.

    El coste es muy alto, €4.300 cada mes pero el cáncer de próstata metastásico diseminado que sufre mi padre no tiene precio.

    Espero que os haya ayudado.

  12. Julio:

    ¿Está seguro de que el medicamento que está recibiendo por su padre realmente es abiraterone? Yo no sabía que este medicamento está disponible aún en cualquier parte del mundo.

  13. Dear Sitemaster:

    My husband has been previously treated with docetaxel, carboplatin, Nizoral, Xeloda,and now with Jevtana. We would like to know if he can benefit from abiraterone. His PSA has been going down since 7 months ago with Jevtana and Xeloda. His PSA is now down to 700 from a high of 1570 ng/ml in November 2010, but we are afraid it may go up again when Jevtana no longer works. His blood tests are OK, weight stable at 83 kilos but we are concerned about a CT scan and an MRI of his head that show diffuse prostate cancer metastasis. We do not know if these skull mestastases have been sitting there since 2.5 years ago when his prostate cancer returned after his prostatectomy (in 2003) because until recently he never had a CT scan and MRI of his head.

    Otherwise he is a physically healthy person. His brain works excellently at 71 years of age, in spite of his chemo-brain. He now takes fish oil capsules to deal with muscle loss. I am well-informed about proper nutrition for advanced prostate cancer. He does pyhsiotherapy exercises daily.

    He has been on chemotherapy since October 2009 — 2.5 years by now. Should he get off chemotherapy now and try abiraterone when Jevtana no longer works for him?

  14. Dear Soledad:

    I have forwarded your qwuestion to “Ask Arthur” on this site. Please click here to find your question and Arthur’s reply, which should be avaiklable some time later today.

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