Abiraterone acetate may help to eliminate cancer prior to surgery in some men with high-risk, localized disease


According to the abstract of a paper to be presented at the upcoming meeting of the American Society for Clinical Oncology in Chicago at the beginning of June, 24 weeks of treatment with neoadjuvant abiraterone acetate + prednisone + an LHRH agonist appears to be able to eliminate visible risk of prostate cancer in post-surgical specimens in a small percentage of men diagnosed with high-risk disease.

This paper by Taplin et al. is based on a small, randomized, Phase II clinical trial in men scheduled for surgery after initial diagnosis with high-risk prostate cancer (based on the NCCN criteria). Thus, all patients had clinical stage T3/4 disease, or a Gleason score ≥ 3 + 4 = 7, or a PSA level ≥ 20 ng/ml, or a PSA velocity > 2 ng/ml/year.

The trial involved 56 patients who were randomized into two groups as follows:

  • The men in Group A (n = 27) were first treated with 12 weeks of neoadjuvant leuprolide acetate and then with a further 12 weeks of leuprolide acetate + abiraterone acetate + low-dose prednisone.
  • The men in Group B (n = 29) were treated for 24 weeks with neoadjuvant abiraterone acetate + leuprolide acetate + prednisone.
  • All 56 men in Groups A and B were then given a radical prostatectomy following their presurgical treatment.

The short-term outcomes of the study showed that:

  • Among the men in Group B
    • 3/29 patients (10 percent) exhibited complete elimination of any pathological evidence of cancer in the post-surgical specimen.
    • 7/29 patients (24 percent) exhibited a disease reduction to ≤ 5 mm of residual cancer in the post-surgical specimen.
    • 7/29 patients (24 percent) exhibited positive lymph nodes at time of surgery.
  • Among the men in Group A
    • 1/27 patients (4 percent) exhibited complete elimination of any pathological evidence of cancer in the post-surgical specimen.
    • 3/27 patients (11 percent) exhibited a disease reduction to ≤ 5 mm of residual cancer in the post-surgical specimen.
    • 3/27 patients (11 percent) exhibited positive lymph nodes at time of surgery.
  •  Treatment was well-tolerated in both groups, with “very low systemic side effects and no additional surgical toxicities.”

According to Dr. Taplin, in quotations appearing on the OncLive web site, the historical rates of complete pathologic remission of prostate cancer (based on the use of standard forms of hormone therapy) are < 5 percent, “So these rates are very impressive.”

The “New” Prostate Cancer InfoLink would caution that this is still only a small trial, and — while these data are interesting — we will need significantly more data before a compelling argument could be made that all men with high-risk, localized prostate cancer should be receiving neoadjuvant treatment with a period of combination hormonal therapy prior to first-line therapy (with surgery or any other first-line. therapy). In particular, we draw the reader’s attention to the fact that, despite the lowering of risk for pathological evidence of cancer in the prostate among the men in Group B compared to Group A, the risk for positive lymph nodes apparently remained higher in Group A compared to Group B.

It should be noted that an analogous trial has been scheduled to study the use of enzalutamide (MDV3100) alone vs. + an LHRH agonist + dutasteride in pre-surgical treatment of men with intermediate- and high-risk prostate cancer, and that the structure of this trial is also reported in the ASCO abstracts.

6 Responses

  1. These results are important for two reasons.

    First, they show the clinical utility of neoadjuvant Zytiga, which should work just as well without the Lupron. In a third of patients a significant reduction in tumour size was seen and a tenth of patients had no sign of cancer at surgery. Perhaps in responses like this surgery may in future be deemed unnecessary.

    Second, this study shows the utility of low-dose prednisone at 5 mg daily. This dose of prednisone was found to offset the corticosteroid imbalance imposed by Zytiga but reduce the side effects seen from prednisone at the usual dose of 10 mg daily.

  2. This year’s ASCO abstracts are looking very interesting but some are yet to be released — such as the Phase III trial results of abiraterone in the pre-chemotherapy setting.

  3. The “New” Prostate Cancer Infolink is the only prostate cancer information service on the web that put the finger on the weak points of the study. Thank you for the good job!

    First, it is a very small trial and there is no statistical significance between the subgroups and for the hypothesis that abiraterone/Zygita can eradicate prostate cancer, as published in the general media. Second, the risk for positive lymph nodes remained higher in men in Group A with 24 weeks on abiraterone/Zygita.

    And not to forget, the researchers in the trial have reported financial ties to the manufacturer of Zygita.

    Much “to do,” about not too much?

  4. Thanks for noticing Gunterman!

    :O)

  5. Is there evidence that abiraterone (or another testosterone-lowering drug) shrinks the prostate and makes surgery more successful? Could that happen here? It seems a smaller gland would make removal more successful and positive margins less common, though EPE or ECE could still exist.

  6. That was part of the theory behind the use of LHRH agonists prior to surgery in the 1990s. It actually made the surgery more difficult, and there was never any evidence to suggest that it made the outcome after surgery any more successful.

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