Using low-dose abiraterone acetate with food (or a standard dose with no food)

We have known for some time that abiraterone acetate 250 mg, when given with food, appears to have activity that may — in at least some patients — be comparable to the activity of abiraterone acetate 1,000 mg given without food. However, we should immediately be clear that the latter is the standard dose regimen used in all major (Phase III), pivotal clinical trials of abiraterone acetate (Zytiga) conducted to date.

Recently, Szmulewitz et al. reported the results of a prospective, randomized, pilot, Phase II study of low-dose abiraterone with a low-fat breakfast as compared to the standard dose in men with castration-resistant prostate cancer.

This was a small trial in just 72 patients, with 36 patients being randomized to the low-dose arm with a food and 36 patients to the standard-dose arm with no food.

The key data reported by Szmulewitz et al. were these:

  • At 12 weeks,
    • The impact on patients’ PSA levels was greater in the low-dose arm than in the standard dose arm.
    • Non-inferiority of the low-dose regimen compared to the standard-dose regimen was established (based on predefined criteria).
  • The PSA response rates were
    • 58 percent in the low-dose arm
    • 50 percent in the standard-dose arm
  • Average (median) progression-free survival was ~ 9 months in both groups.
  • Androgen levels (testosterone and dihydrotestosterone) decreased similarly in both arms.
  • Serum concentrations of abiraterone acetate were greater in patients treated with the standard dose.
  • There were possibly meaningful differences in the spectrum of adverse effects between the two dosing regimens

The paper appears to have stirred a real controversy within the medical oncology community.

The following follow-up articles and other commentaries have now appeared on line:

The “New” Prostate Cancer InfoLink does not believe that, looking at the available data and opinions, there is necessarily a right or a wrong answer to the question being raised, which is, basically:

Can low-dose abiraterone be given with food as safely and as effectively as the currently standard and approved dose of abiraterone given without food?

We also do not believe that the US Food and Drug Administration (FDA) can require the manufacturer to implement a Phase III trial to answer this question. But …

Abiraterone acetate is now a widely used drug and if using significantly less of the drug can be as effective and safe as using the currently approved dose, perhaps the other question is whether it is in the interests of the US government and others (CMS and commercial payers) to conduct an appropriate, independent, comparative Phase III trial through the auspices of the National Cancer Institute. The manufacturer might even consider that it would be politically wise to offer to provide free drug for the conduct of such a trial.

3 Responses

  1. In January 2018, J&J’s abiraterone patent was invalidated by the U.S. Patent Trial and Appeal Board, which may open up generic competition as early as this year. I’m not aware of J&J successfully appealing that ruling. Generic copies of abiraterone would likely lower the cost of the drug even more than one might expect from using the lower dose.

  2. Dear Len:

    While it is true that generic access to abiraterone acetate may well lower the costs associated with abiraterone treatment in the next 2 years, if there is no need to be taking 1,000 mg without food when one could be taking 250 mg with food, that has benefits in relation to biology, biochemistry, convenience, and compliance — as well as cost.

  3. I recently chose to take “two” 250 mg abiraterone/Zytiga tablets daily with food to determine if this would be as effective as the four 250 mg/1,000 mg total daily. My PSA has gone down slightly from a high of 2.77 ng/ml to a current 2.00 ng/ml, but since i also just had targeted radiation following fluciclovine/Axumin imaging identifying the only small amount of cancer cell activity found close to my the area of my anastomosis (carried out saveral years ago), I cannot be certain if this PSA drop is from the continuing abiraterone but in different low dosage with food, or resulting from the fractured DNA as it slowly disperses following the targeted radiation.

    In my opinion, the finding of abiraterone with a single 250 mg tablet daily with food (and continued 5 mg prednisone twice daily) would be a huge expense saver to CMS and other insurers as well as to those patients who must pay out-of-pocket. Obviously not a choice of the manufacturer with certain loss of revenue.

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