Safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel: expanded access in North America

Anthony M Joshua, Neal D Shore, Fred Saad, Kim N Chi, Carl A Olsson, Urban Emmenegger, Mark Scholz, William Berry, Som D Mukherjee, Eric Winquist, Naomi B Haas, Margaret A Foley, Carl Dmuchowski, Frank Perabo, Mohammad Hirmand, Nahla Hasabou, Dana Rathkopf, Enzalutamide Expanded Access Study Investigators, Anthony M Joshua, Neal D Shore, Fred Saad, Kim N Chi, Carl A Olsson, Urban Emmenegger, Mark Scholz, William Berry, Som D Mukherjee, Eric Winquist, Naomi B Haas, Margaret A Foley, Carl Dmuchowski, Frank Perabo, Mohammad Hirmand, Nahla Hasabou, Dana Rathkopf, Enzalutamide Expanded Access Study Investigators

Abstract

Background: The open-label, single-arm enzalutamide expanded access program (EAP) in the United States and Canada evaluated the safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel.

Methods: Patients (n = 507) received enzalutamide 160 mg/day until disease progression, intolerable adverse events (AEs), or commercial availability occurred. AEs and other safety variables were assessed on day 1, weeks 4 and 12, and every 12 weeks thereafter. Data following transition to commercial drug were not collected.

Results: Median age was 71 years (range 43-97); 426 patients (83.9%) had a baseline ECOG score of ≤1. In addition to docetaxel, the majority of patients had received prior prostate cancer treatments such as abiraterone (76.1%) or cabazitaxel (28.6%). Median study treatment duration was 2.6 months (range 0.03-9.07). The most frequently reported reasons for discontinuation were commercial availability of enzalutamide (46.7%) and progressive disease (33.7%). A total of 88.2% of patients experienced AEs; 45.4% experienced AEs with a maximum grade of 1 or 2. Fatigue (39.1%), nausea (22.7%), and anorexia (14.8%) were the most commonly reported AEs. Seizure was reported in four patients (0.8%). The most commonly reported event leading to death was progression of metastatic prostate cancer (7.7%).

Conclusion: In this heavily pretreated EAP population with progressive mCRPC, enzalutamide was well tolerated and the safety profile was consistent with that of the AFFIRM trial.

Trial registration: ClinicalTrials.gov NCT01606982.

Keywords: enzalutamide; expanded access program; metastatic castration-resistant prostate cancer; safety; treatment exposure.

© 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Patient flow diagram.

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