CHICAGO, IL— Combination androgen blockade with enzalutamide plus androgen biosynthesis inhibition with abiraterone acetate (AA) is safe for men with bone-metastatic castration resistant prostate cancer (mCRPC), according to findings from a safety and pharmacokinetic study presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
The combination “has a favorable safety profile, without clinically meaningful PK DDI [pharmacokinetic drug-drug interactions],” reported lead study author Eleni Efstathiou, MD, and coauthors at the Alexandra General Hospital of Athens, in Greece. “No unexpected side effects were observed and there was no evidence of clinically meaningful drug-drug interaction. …This combination can be developed safely and limiting pharmacokinetic interactions are not anticipated”
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“Feedback mechanisms observed by either agent are dissipated,” Dr. Efstathiou reported. “These promising findings are indicative of more efficacious androgen signaling inhibition in men with mCRPC.”
A total of 60 study participants were treated with enzalutamide (160 mg once daily) and AA (1 g once daily) plus prednisone (5 mg daily). Of these participants, 13% had prior chemotherapy, which a post-hoc analysis found to be associated with less benefit from this combination treatment, Dr. Efstathiou noted.
“There were no drug-related deaths,” Dr. Efstathiou said. “There were no new safety concerns.”
A total of 11 patients (18%) discontinued the combination treatment within 4 months, because of disease progression. These patients were deemed to have primary resistance, as evidenced by a lack of PSA decline.
No grade 4 adverse events (AEs) were reported. Grade 3 treatment-related AEs included alanine transaminase increase (six patients), hypertension (eight patients), alkaline phosphatase rise (four patients), arthralgia (three patients), and bone pain (two patients).
AA exhibited no clinically-relevant impact on enzalutamide pharmacokinetics, Dr. Efstathiou said.
- Efstathiou E, Titus MA, Wen S et al. Abstract 5000. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.