Responses to abiraterone + prednisone after docetaxel and enzalutamide in men with mCRPC


Two new papers offer us some preliminary information about the activity of abiraterone acetate in men with metastatic, castration-resistant prostate cancer (mCRPC) after prior treatment with docetaxel-based chemotherapy and with enzalutamide.

There are currently at least five outstanding and important questions about the clinical use of abiraterone acetate and enzalutamide in the treatment of men with mCRPC:

  • In men who are chemotherapy-naive, does giving abiraterone + predisone before enzalutamide affect the response to enzalutamide, and if so how much?
  • In men who are chemotherapy-naive, does giving enzalutamide before abiraterone + predisone affect the response to abiraterone + prednisone, and if so how much?
  • In men who have already received docetaxel-based chemotherapy, does giving abiraterone + predisone before enzalutamide affect the response to enzalutamide, and if so how much?
  • In men who have already received docetaxel-based chemotherapy, does giving enzalutamide before abiraterone + predisone affect the response to abiraterone + prednisone, and if so how much?
  • Is giving enzalutimide together with abiraterone + prednisone before or after chemotherapy more effective than giving the two drugs sequentially.

Two recent papers in Annals of Oncologyone by by Noonan et al. and the other by Loriot et al. — offer some pilot data addressing the fourth of these five questions.

The paper by Noonan et al. is based on a retrospective review of data from 30 patients with mCRPC at four clinical centers in the USA and Canada. According to this study:

  • All 30 patients had received prior treatment with docetaxel-based chemotherapy and enzalutamide monotherapy.
  • Average (median) patient age at initiation of abiraterone acetate was 70 years (range, 56 to 84 years)
  • 21/30 patients (70 percent) had an ECOG performance status of 0 or 1.
  • The median duration of prior enzalutamide treatment was 41 weeks (range, 6 to 95 weeks).
  • 21/30 patients (70 percent) had responded to enzalutamide with a PSA decrease of ≥ 30 percent from baseline.
  • The median duration of abiraterone + prednisone treatment was 13 weeks (range, 1 to 52 weeks).
  • There were no objective radiographic responses to abiraterone acetate.
  • Median time to progression on abiraterone + prednisone was 15.4 weeks.
  • Median overall survival  from initiation of abiraterone was 50.1 weeks.
  • 3/30 patients (10 percent) responded to abiraterone + prednisone with a PSA decrease of ≥ 30 percent from baseline
  • Of these three patients, two had demonstrated PSA progression as best response with prior enzalutamide.

The paper by Loriot et al. is based on an analogous retrospective review of data from 38 patients with mCRPC at an unspecified number of European centers. According to this study:

  • All 38 patients had received prior treatment with docetaxel-based chemotherapy and enzalutamide monotherapy.
  • Average (median) patient age at initiation of abiraterone acetate was 71 years (range, 52 to 84 years).
  • The abstract offers us no data on prior duration of enzalutamide treatment or responses to enzalutamide treatment.
  • Metastatic sites included bone in 37/38 patients (97 percent), lymph nodes in 15/38 patients (39 percent), and viscera in 10/38 patients (26 percent).
  • 3/38 patients (8 percent) responded to abiraterone acetate + prednisone with a PSA decrease of ≥ 50 percent after ≥ 4 weeks.
  • 7/38 patients (18 percent) responded to abiraterone acetate + prednisone with a PSA decrease of ≥ 30 percent after ≥ 4 weeks.
  • Median progression-free survival (PFS) after treatment with abiraterone acetate + prednisone was 2.7 months.
  • 12 patients underwent radiologic assessment and 1/12 (8 percent) exhibited a confirmed partial response.

In both of these studies, it seems clear that treatment of men with mCRPC with docetaxel-based chemotherapy and then with enzalutamide does significantly affect the potential for response to abiraterone + prednisone — but does not absolutely preclude a meaningful clinical response in about 10 to 20 percent of patients. What we need to know now is whether the outcome is different in men with mCRPC who have docetaxel-based chemotherapy followed by abiraterone + prednisone and then enzalutamide. In other words, can enzalutamide work better after abiraterone + prednisone than the other way around (at least in the men who have already had chemotherapy).

Ideally, of course, one would like to see a randomized trial of the sequencing of abiraterone + prednisone vs. enzalutamide in men with mCRPC before and after docetaxel-based chemotherapy. However, the chances of such a trial being implemented in the near future would seem to be extremely small.

2 Responses

  1. In your paragraph following the first set of bullets, I think you meant to write, “… — offer some pilot data addressing the fourth of these five questions.”

    Also, I had two questions more linguistic than technical.

    You quote Noonan et al. as reporting, “Median time to progression on abiraterone + prednisone was 15.4 weeks.” You quote Loriot et al. as reporting, “Median progression-free survival (PFS) after treatment with abiraterone acetate + prednisone was 2.7 months.” Is there any reason not to say, “107.8 days” and “82.1 days”?

    What is the difference, if any, between “median time to progression” and “median progression-free survival“? (Perhaps one but not the other factors in death from other causes?)

    Otherwise, an excellent summary of the two papers.

  2. Dear Paul:

    (1) You are correct. It should have been “fourth”, not “third”, and it has been duly corrected.

    (2) The times to progression and to progression-free survival are quoted above exactly as given in the original papers. However, if you want to convert these to 108 and 82 days respectively, those are probably close enough. I wouldn’t bother with the tenths of days!

    (3) The distinction between median time to progression and median progression-free survival is probably negligible given the limited follow-up in these two studies. They are technically slightly different (and it is impossible to know exactly how different without being able to read the section on materials and methods in each of the two papers), but for the purposes of general judgment in two small, retrospective studiers like this you can probably consider them to be analogous.

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