(ChemotherapyAdvisor) – The novel, second-generation antiandrogen receptor, ARN-509, is safe and well tolerated in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC), with promising preliminary activity based on high prostate-specific antigen (PSA) response rates, according to results of a study presented during the 4th annual Genitourinary Cancers Symposium in Orlando, FL.

Preliminary results for men with high-risk nonmetastatic CRPC, one of three patient cohorts from the phase 2 portion of a multicenter phase 1/2 study evaluating the activity of ARN-509, showed that 12-week PSA response was 91% and time to PSA progression had not been reached, noted Matthew R. Smith, MD, PhD, Director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center, Boston, MA, and colleagues. The other two cohorts being studied are metastatic treatment-naïve CRPC and progressive disease after abiraterone acetate.

The study enrolled 47 patients between November 2011 and May 2012. Median age was 71 years (range, 51 to 88 years). At baseline, Eastern Cooperative Oncology Group performance status was 0 in 77% of patients, Gleason Score 8-10 in 32%, and median PSA was 10.7 ng/mL. All patients had received prior treatment with a luteinizing hormone-releasing hormone (LHRH) analog with or without a first-generation antiandrogen.

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“All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes < 3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months,” the investigators stated.

As established in the phase 1 portion of the study, ARN-509 was administered at a dose of 240 mg per day. The primary end point was PSA response rate at 12 weeks, according to Prostate Cancer Working Group 2 Criteria. Secondary end points included safety, time to PSA progression, and 1-year metastasis-free survival. Every 4 weeks, PSA assessments were collected and, every 16 weeks, tumor scans performed.

Three patients discontinued the study at median treatment duration of 20 weeks. The most common treatment-related adverse events (AEs) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). Incidence of grade 3 AEs was 6.4% and no seizures have been observed.

ARN-509 binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding.

The 2013 Genitourinary Cancers Symposium is co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).


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