Low-Dose Abiraterone With Food vs Standard-Dose Abiraterone in Castration-Resistant Prostate Cancer
In a phase II trial reported in the Journal of Clinical Oncology, Szmulewitz et al found that low-dose abiraterone (Zytiga) given with a low-fat meal was noninferior to standard-dose abiraterone in the fasting state with regard to reduction in prostate-specific antigen (PSA) levels among patients with castration-resistant prostate cancer.
Study Details
In the open-label study, 72 patients with progressive disease from 7 sites in the United States and Singapore were randomized between January 2012 and March 2016 to receive low-dose abiraterone at 250 mg with a low-fat meal (n = 36) or standard-dose abiraterone at 1,000 mg in the fasting state (n = 36). Both groups received prednisone at 5 mg twice daily.
Log change in PSA at 12 weeks was the primary endpoint, with a noninferiority design for comparison of outcomes.
PSA Responses
At 12 weeks, the magnitude of reduction in PSA from baseline to 12 weeks was greater in the low-dose group, with mean log changes of –1.59 vs –1.19 in the standard-dose group. The upper one-sided 90% confidence limit for the difference between the two groups was 0.11 (standard deviation = 0.068), satisfying the predetermined criterion for noninferiority.
Rates of PSA response, defined as ≥ 50% reduction after 12 weeks, were 58% vs 50%. Median progression-free survival was 8.6 months in both groups (P = .38). Decreases in androgen levels were similar in the two groups. Abiraterone concentrations were higher in the standard-dose group (P < .001).
Adverse Events
The most common adverse events of any grade in both the low-dose and standard-dose groups were fatigue (47% vs 47%), pain (44% vs 27%), and hypertension (24% vs 34%). Grade ≥ 3 adverse events were more common in the low-dose groups (32% vs 18%, P = .26). Grade ≥ 3 adverse events of interest consisted of hypertension (5.9%) and diarrhea (2.9%) in the low-dose group and hypokalemia (2.9%) in the standard-dose group
The investigators concluded, “Low-dose [abiraterone acetate] (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.”
The study was supported in part by grants from the National Cancer Institute.
Russell Z. Szmulewitz, MD, of The University of Chicago, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
