AA plus Prednisone 5 Mg Effective in Lowering PSA in Men with nmCRPC

New Orleans—In patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC), treatment with abiraterone acetate (AA) plus 5 mg of prednisone is very effective in lowering prostate-specific antigen (PSA). That was the primary finding of a phase 2, multicenter study conducted by Charles J. Ryan, MD, and colleagues. The researchers presented study results during a session at the AUA 2015 Annual Meeting.

Patients with nmCRPC will eventually progress to mCRPC. There is no currently approved therapy available for nmCRPC. This study was designed to assess the ability of AA in combination with 5 mg of prednisone to decrease levels of PSA in patients with nmCRPC and rising PSA.

At screening, all study participants had nmCRPC but also had clinical features that placed them at higher risk of developing mCRPC: PSA value ≥10 ng/mL or PSA doubling time ≤10 months. Participants received AA 1000 mg plus prednisone 5 mg daily; each treatment cycle was 28 days. PSA response rate at 6 months was the primary end point. Secondary end points included change in testosterone levels, time to PSA progression, time to radiographic disease progression, and safety. Assessment of PSA and imaging scans were conducted every 3 months.

During the study period of May 2011 to July 2013, 131 patients at 38 sites in the United States were enrolled in the study. Data cutoff for the current analysis was December 31, 2013. Median age was 72 years; median baseline PSA was 11.9 ng/mL. Of the 131 patients, 122 were evaluable for the analysis of PSA response.

By the end of six cycles of treatment, 106 of the 122 patients (87%) had ≥50% reduction in PSA and 73 of the 122 (60%) had ≥90% PSA reduction. Twenty-three patients (17.6%) experienced PSA progression.

PSA progression-free rates were 82.4% at 12 months, 73.5% at 18 months, and 62.8% at 24 months. At the time of data cutoff, median time to PSA progression was not estimable.

Radiographic progression-free survival rates were 89 at 12 months, 87 at 18 months, and 87 at 24 months. Mean testosterone levels were reduced by approximately 96% following three and six cycles of study treatment.

Adverse events (AEs) were reported in 92.4% of patients; 43.6% had a grade 3 or higher AE. Serious AEs were reported in 10.7% of patients; 27.5% had a serious AE of grade 3 or higher. Discontinuation of study treatment due to AEs was observed in 10.7% of patients.

Four patients had AEs that resulted in death: coronary artery disease, myocardial infarction, acute respiratory failure, and pneumonia. At the time of presentation, no patient has had prednisone dose increased to >5 mg to manage symptoms of mineralocorticoid excess.

“In men with high-risk nmCRPC, treatment using AA+P5 is very effective in lowering PSA. The rate and depth of PSA decline appear superior to men with mCRPC. The safety profile in this trial using prednisone 5 mg is consistent with previously reported data using 10 mg prednisone daily,” the authors said.

Source: Ryan CJ, Crawford ED, Shore ND, et al. Effect of abiraterone acetate and low dose prednisone on prostate-specific antigen in patients with non-metastatic castration-resistant prostate cancer: The results from impact of abiraterone acetate in prostate-specific antigen core study. Abstract of a presentation at the American Urological Association 2015 Annual Meeting, New Orleans, Louisiana, May 19, 2015.