Analysis of European Patients Enrolled in a Global Early Access Protocol with Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer Progressing After Chemotherapy

Abstract

INTRODUCTION & OBJECTIVES: In the final analysis of COU-AA-301, the pivotal phase 3 randomized trial of post-chemotherapy patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate (AA) + prednisone/prednisolone (P) significantly prolonged median overall survival by 4.6 months in post-docetaxel mCRPC patients, with a 26% reduction (hazard ratio = 0.74 [95% confidence interval (CI), 0.64-0.86]; p < 0.0001) in the risk of death vs P alone. Following release of COU-AA-301 data, a global early access protocol (EAP) was opened to enable preapproval access to AA for mCRPC patients who had progressed after chemotherapy and for whom no approved alternative treatment was available. We report the outcomes from patients in the EAP who were enrolled from 10 countries in Europe. MATERIAL & METHODS: Globally, 2314 mCRPC patients were enrolled and 98.4% of patients had previously received docetaxel. Of those enrolled, 1171 (51%) were European. Patients received AA (1000 mg/d PO) + P (5 mg bid) and continued on the EAP until disease progression, dosing noncompliance, sustained side effects, administration of prohibited medications, or until AA became available and reimbursed in the respective country. The primary end point was the number of clinically important adverse events (AEs), including ≥ grade 3 or serious AEs (NCI-CTCAE v 4.0) occurring during treatment and within 30 days of treatment discontinuation. Prostate-specific antigen (PSA) progression and clinical progression assessments were used to guide treatment decisions. RESULTS: The median age of European patients was 71 years. 90% and 39% of patients had bone and soft-tissue metastases, respectively. Median duration of therapy was 6.4 months. Median time to PSA progression (385 events) was 9.3 months (95% CI, 8.5-11) and median time to clinical progression (412 events) was 13 months (95% CI, 12-14.8). Grade 3/4 AEs of special interest were hepatotoxicity (6.7%), hypertension (5.1%), cardiac disorders (1.5%), osteoporosis (1.1%), fluid retention/edema (0.9%), and hypokalemia (0.8%). The EAP investigator-reported study discontinuation rates due to AEs and death in European patients were 7.4% and 8%, respectively. Sponsor assessment of the cause of these deaths was disease progression (3.9%), unrelated adverse experience (3.2%), and unknown (0.9%). CONCLUSIONS: The safety results of European patients in the EAP are consistent with those of the overall EAP population and with those from the pivotal COU-AA-301 trial. No new safety signals were reported.