Preliminary results of a Phase II trial of ARN-509 in CRPC


We have previously discussed the early development of ARN-509 as a novel, second-generation, antiandrogenic agent for the potential treatment of men with advanced prostate cancer.

At the Genitourinary Cancer Symposium today, Smith et al. presented data from the Phase II portion of the  multicenter Phase I/II study in evaluating the activity of ARN-509 in three patient populations of men with castration-resistant prostate cancer (CRPC):

  • High-risk, non-metastatic CRPC
  • Metastatic, treatment-naïve CRPC
  • Progressive disease after prior treatment with abiraterone acetate

In this study, all patients had CRPC, with no radiographic evidence of metastases and high risk for disease progression based on a PSA value ≥ 8 ng/ml within 3 months of enrollment and/or a PSA doubling time ≤ 10 months.

The patients were all treated with ARN-509 at the recommended Phase II dose of 240 mg/day. The primary endpoint was a PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 criteria. Secondary endpoints included safety, time to PSA progression, and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks.

Here is a summary of the study results:

  • 47 patients were enrolled between November 2011 and May 2012.
  • The average (median) age of the patients was 71 years (range, 51 to 88).
  • At baseline, patients presented with
    • An ECOG performance status of 0 (77 percent)
    • A Gleason score of 8 to 10 (32 percent)
    • A median PSA of 10.7 ng/ml.
  • All patients had received prior treatment with an LHRH analog with or without a first-generation anti-androgen.
  • At a median treatment duration of 20 weeks, 3/47 patients (6 percent) discontinued the study.
  • The most common treatment-related adverse events (AEs) were
    • Fatigue (30 percent)
    • Diarrhea (28 percent)
    • Nausea (17 percent)
    • Rash (13 percent)
    • Abdominal pain (11 percent).
  • The incidence of Grade 3 AEs was 6.4 percent, and no seizures have been observed to date.
  • The 12-week PSA response was 91 percent.
  • Time to PSA progression has not been reached.

Smith et al. conclude that ARN-509 is safe and effective in men with high-risk, non-metastatic CRPC,  and that it has promising activity based on high PSA response rates.

The results of randomized Phase III trials will be needed to demonstrate whether ARN-509 really is a valuable therapeutic agent in the treatment of late-stage prostate cancer

2 Responses

  1. Did they present results from the other two groups?

    — Metastatic, treatment-naïve CRPC
    — Progressive disease after prior treatment with abiraterone acetate

  2. Not that I am aware of Jake, but look at the long list of posters in this link. There were two that dealt with ARN-509.

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