Everolimus + bicalutamide in treatment of CRPC?

A small, single-institution, Phase II clinical trial has suggested the possibility that everolimus + bicalutamide may have useful activity in the treatment of some men with castration-resistant prostate cancer. However, it is already evident that the dose of everolimus used in this trial was probably too high.

Pan et al. first reported these findings at the Genitourinary Cancers Symposium in 2014. The final study report has now been published in Cancer (see also this report in Renal & Urology News).

The trial was focused on patients who had progressive CRPC with a serum testosterone level of < 50 ng/ml, who had not previously been treated, long-term, with bicalutamide (Casodex), and who had not been treated with everolimus (Afinitor). Patients could have received bicalutamide for short-term prevention of the flare reaction at initiation of androgen deprivation therapy (ADT).

All patients were initially treated with oral bicalutamide 50 mg and oral everolimus 10 mg, both once daily, on a 4-week-long cycle.

Here are the basic study results:

  • 24 patients were enrolled into the study
  • Average (mean) age was 71.1 years (range, 53.0 to 87.0 years).
  • Average (mean) PSA level at study entry was 43.4 ng/dl (range, 2.5 to 556.9 ng/dl).
  • Average (mean) length of treatment was 8 cycles (range, 1.0 to 23.0 cycles).
  • 18/24 patients (75 percent) showed a PSA decrease of 30 percent or more.
  • 15/24 patients (63 percent) showed a PSA decrease 50 percent or more.
  • Median overall survival was 28 months.
  • 14/24 patients (54 percent) exhibited grade 3 (13 patients) or grade 4 (1 patient with sepsis) adverse events that were attributable to treatment.

The results reported by Pan et al. conflict with the results of another, similar phase II trial reported in 2012 by Nakabayashi et al. However, most of the patients in the previously reported study were not bicalutamide-naive.

Whether the combination of bicalutamide + everolimus would be an effective treatment in men who are bicalutamide-naive but have had prior exposure to either abiraterone acetate (Zytiga) or enzalutamide (Xtandi) seems to be an unanswered question, and so the clinical value of this form of treatment is still unknown at the present time. What is clear is that the initial daily dose of everolimus being used in this trial was higher than most patients could tolerate, and so if the combination is to be tested again it would be essential to start therapy with a somewhat lower dose of the everolimus.

One Response

  1. I read very recently that men with PTEN loss respond well to everolimus. Would be interesting to run a corellation on this sample!

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