Low-Dose Prednisone Associated with Low Incidence of Corticosteroid-Associated AEs

New Orleans—Abiraterone acetate (AA) is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis, prolonging survival of patients with metastatic castration-resistant prostate cancer (mCRPC). When AA is administered to mCRPC patients, a low dose of prednisone is also given.

Long-term use of a moderate- or high-dose corticosteroid has an established adverse event (AE) profile. A recent analysis was conducted to determine whether long-term use of low-dose prednisone with or without AA led to corticosteroid-associated AEs. Leonard G. Gomella, MD, and colleagues presented results of the study during a session at the AUA 2015 Annual Meeting.

The analysis included 2267 patients with mCRPC in the COU-AA-301 and COU-AA-302 trials who received 5 mg twice a day of prednisone, representing 2006 patient-years of prednisone exposure. Of those, 1333 patients receivoed AA and prednisone. The researchers used an inclusive Standardized MedDRA Queries-riented approach to identify 112 preferred terms for known corticosteroid-associated AEs from both databases. They assessed corticosteroid-associated AEs during each 3-month exposure interval and across all exposure to prednisone.

The overall incidence of corticosteroid-associated AEs for any prednisone exposure was 25% for all patients; 26% for AA and prednisone; and 23% for prednisone alone. The incidence of grade 3 or higher corticosteroid-associated AEs with any prednisone exposure was 5% for all patients, 5% for AA and prednisone, and 4% for prednisone alone.

The most common grade 3 or higher corticosteroid-associated AEs occurring in ≥0.1% of all patients were hyperglycemia (2%), cataract (0.4%), diabetes mellitus (0.4%), gastrointestinal hemorrhage (0.3%), adrenal insufficiency (0.1%), hip fracture (0.1%), melena (0.1%), and osteoporotic spinal compression fracture (0.1%). The overall incidence of weight increase (grade 1 and 2 only) was 4% for all patients, 4% for AA plus prednisone, and 5% for prednisone alone. Most were grade 1 (3.4%).

When duration of exposure was used in the assessment, (range, 3-month intervals up to ≥30 months), grade 3 or higher corticosteroid-associated AEs fluctuated between 1% and 2%. However, no discernable trend was seen. The observed change in weight from baseline had no apparent increase over time.

“With over 2000 patient-years of exposure, low-dose prednisone given with or without AA is associated with an overall low incidence of corticosteroid-associated AEs. The occurrence of corticosteroid-associated AEs remained low with increased duration of exposure to prednisone,” the researchers said.

Source: Gomella LG, Chi KN, deBono JS, et al. Assessment of corticosteroid (CS)-associated adverse events (AEs) with long-term (LT) exposure to low-dose prednisone (P) given with abiraterone acetate (AA) to metastatic castration-resistant prostate cancer (mCRPC) patients (pts). Abstract of a presentation at the American Urological Association 2015 Annual Meeting, New Orleans, Louisiana, May 19, 2015.