Prospective International Randomized Phase II Study of Low-Dose Abiraterone With Food Versus Standard Dose Abiraterone In Castration-Resistant Prostate Cancer

Purpose Abiraterone acetate (AA) is a standard of care for metastatic castration-resistant prostate cancer (CRPC). Despite a large food effect, AA was administered under fasting conditions in its pivotal trials. We sought to test the hypothesis that low-dose AA (LOW; 250 mg with a low-fat meal) would have comparable activity to standard AA (STD; 1,000 mg fasting) in patients with CRPC. Patients and Methods Patients (n = 72) with progressive CRPC from seven institutions in the United States and Singapore were randomly assigned to STD or LOW. Both arms received prednisone 5 mg twice daily. Prostate-specific antigen (PSA) was assessed monthly, and testosterone/dehydroepiandrosterone sulfate were assessed every 12 weeks with disease burden radiographic assessments. Plasma was collected for drug concentrations. Log change in PSA, as a pharmacodynamic biomarker for efficacy, was the primary end point, using a noninferiority design. Progression-free survival (PFS), PSA response (≥ 50% reduction), change in androgen levels, and pharmacokinetics were secondary end points. Results Thirty-six patients were accrued to both arms. At 12 weeks, there was a greater effect on PSA in the LOW arm (mean log change, -1.59) compared with STD (-1.19), and noninferiority of LOW was established according to predefined criteria. The PSA response rate was 58% in LOW and 50% in STD, and the median PFS was approximately 9 months in both groups. Androgen levels decreased similarly in both arms. Although there was no difference in PSA response or PFS, abiraterone concentrations were higher in STD. Conclusion Low-dose AA (with low-fat breakfast) is noninferior to standard dosing with respect to PSA metrics. Given the pharmacoeconomic implications, these data warrant consideration by prescribers, payers, and patients. Additional studies are indicated to assess the long-term efficacy of this approach.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 Mar 28 [Epub ahead of print]

Russell Z Szmulewitz, Cody J Peer, Abiola Ibraheem, Elia Martinez, Mark F Kozloff, Bradley Carthon, R Donald Harvey, Paul Fishkin, Wei Peng Yong, Edmund Chiong, Chadi Nabhan, Theodore Karrison, William D Figg, Walter M Stadler, Mark J Ratain

Russell Z. Szmulewitz, Abiola Ibraheem, Elia Martinez, Mark F. Kozloff, Chadi Nabhan, Theodore Karrison, Walter M. Stadler, and Mark J. Ratain, The University of Chicago, Chicago; Mark F. Kozloff, Ingalls Hospital, Harvey; Paul Fishkin, Illinois Cancer Care, Peoria, IL; Cody J. Peer and William D. Figg, National Cancer Institute, Rockville, MD; Bradley Carthon and R. Donald Harvey, Winship Cancer Institute of Emory University, Atlanta, GA; and Wei Peng Yong and Edmund Chiong, National University Cancer Institute, Singapore, Singapore.

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