What’s the “best” form of first-line treatment for mHSPC today?

A new paper in the Annals of Oncology has addressed the critical question regarding what might be “the best” way we currently have to start treatment for a man newly diagnosed with metastatic, hormone-sensitive prostate cancer (mHSPC).

Vale et al. carried out a meta-analysis of data from a total of 10 completed trials which had closed to recruitment, and one trial in which recruitment was ongoing. Their results are based on six trials that included a total of 6,204 men (97% of the men randomized in all six completed trials).

The full text of this paper by Vale et al. is freely available on line, but the summary results are as follows:

  • Estimates of effects on overall survival were consistent with reported comparisons with standard ADT alone for
    • ADT + abiraterone acetate + prednisone (hazard ratio [HR] = 0.61)
    • ADT + docetaxel (HR = 0.77)
    • ADT + zoledronic acid + celecoxib (HR = 0.78)
    • ADT + zoledronic acid + docetaxel (HR = 0.79)
    • ADT + celecoxib (HR = 0.94)
    • ADT + zoledronic acid (HR = 0.90) 95% CI 0.79–1.03)
  • The effect of ADT + zoledronic acid + celecoxib is consistent with the additive effects of the individual treatments.

The overall results of this meta-analysis suggest that ADT + abiraterone acetate + prednisone (as used in the LATITUDE and STAMPEDE trials) has the highest probability of being the most effective treatment both for overall survival (94 percent probability) and failure-free survival (100 probability probability). ADT + docetatxel was the second-best treatment of OS (35 percent probability).

Vale et al. conclude as follows:
  • That their results support the first-line use of either ADT + abiraterone acetate + prednisone or ADT + docetaxel in men with mHSPC.
  • That ADT + abiraterone acetate + prednisone appears to be the most effective treatment, but it is not clear to what extent and whether this is due to a true increased benefit with ADT + abiraterone acetate + prednisone or the variable features of the individual trials.

The “New” Prostate Cancer InfoLink would remind patients that long-term treatment with a corticosteroid like prednisone or prednisolone comes with its own set of problems and side effects. There are therefore some significant concerns about the long-term use of ADT + abiraterone acetate + prednisone as a continuous form of treatment for mHSPC.

8 Responses

  1. If the newly approved apalutamide has a better long-term safety profile than abiraterone + prednisone, then it might be a preferred strategy here.

  2. Sitemaster,

    I read the underlying abstract and, unless I missed it, I was disappointed to find that none of the probability tables stated a comparison summary in terms of median months of OS and FFS for each treatment mode. Clearly, that information was available to the authors.

    It would have been very helpful from a patient perspective for the tables to have stated median OS and FFS for each treatment mode. Without independently reviewing the results of each of the underlying trials, I am left wondering whether the best treatment mode resulted in a few weeks or many months OS difference compared to other treatment modes.

    Thanks for your article.

  3. Dear Peter:

    As yet we have no data on the use of apalutamide in the treatment of evidently metastatic (i.e., TxNxM1) HSPC. This product is only approved for the treatment of micrometastatic (i.e., TxNxM0) HSPC.

  4. Dear Richard:

    The published data show that the two “best” forms of treatment for newly-diagnosed mHSPC (ADT + abiraterone + prednisone and ADT + docetaxel) both provided many months of failure-free and overall survival benefit compared to ADT alone. However, there were differences in the structures of the two trials and so it is impossible to make a direct assessment as to whether one of these two type of therapy is really “better” than the other on an absolute basis. That may depend on a variety of patient factors.

    One thing that is certain at the moment is that ADT + abiraterone + prednisone is a great deal more expensive over time than ADT + docetaxel. That difference might disappear quite quickly when abiraterone loses patent protection (which will happen relatively soon).

  5. I was successful for 5 years 8 months following adding Zytiga/abiraterone four 250 mg tablets (1000 mg) daily with prednisone 5 mg twice daily to my continuing Lupron and Avodart 0.5 mg daily when that was showing failure.

    Since that 5 years 8 months my PSA had risen over 1.0 ng/ml heading towards the 2.0n g/ml I had determined years back would be the level my MedOnc and I look to other options. Stopped Zytiga and prednisone, continued Lupron and Avodart and brought on Xtandi/enzalutamide four 40 mg tablets (160mg) daily without much success. More recently went back to Lupron, Avodart, and Zytiga + prednisone, but still with no success since recent PSA was 2.23 ng/ml.

    I had left-over Xtandi so personally decided on my own a trial of Zytiga two 250 mg (500 mg) daily WITH FOOD, prednisone 5 mg twice daily, Xtandi two 40 mg (80 mg) every other day, and continued Lupron and Avodart but cut Avodart to one 0.5 mg capsule every third day since once established in system the use can be spread out to likely even one capsule every fourth day. I will continue this until my Xtandi supply runs out or PSA shows continued elevation. Will see what happens over next few months. I want to avoid chemotherapy as long as possible.

    Imaging is still unable to identify the exact location of tumor activity but without doubt I have mets somewhere (MedOnc believes in bone, but no pain anywhere). If I can save enough money, I may head to Mayo in Rochester, MN, for the C-11 choline PET/CT imaging to see if that is sensitive enough to identify location. That would be wonderful it it did and would hope targeted radiation would then zap any activity.

  6. While we understand that Chuck Maack has many years of experience as an advocate and patient educator, we feel obliged to note that The “New” Prostate Cancer InfoLink cannot and does not endorse this type of experimental self-medication outside a clinical trial and without a physician’s explicit oversight and approval because it can come with very considerable medical risk.

  7. I note that the NHS apparently is not convinced that aberaterone + ADT + prednisone is the “best” treatment mode for mHSPC, following the logic of Sitemaster’s comment above about the relative cost of zytiga compared to docetaxel. (See here.)

    NICE could have saved some research dollars by subscribing to The “New” Prostate Cancer Infolink and asking for Sitemaster’s opinion.

  8. Dear Richard:

    Wisely, I don’t believe NICE comes to conclusions about anything on the basis of one person’s opinions!


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