Positive results from a phase 2 study of enzalutamide (Xtandi, Astellas US/Medivation, Inc.) compared with bicalutamide in patients with metastatic castration-resistant prostate cancer have been published online in Lancet Oncology.
The TERRAIN trial enrolled 375 patients in North America and Europe. The study enrolled patients with metastatic prostate cancer whose disease had progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue or after surgical castration. The study’s primary endpoint was progression-free survival (PFS), defined as the time from randomization to centrally confirmed radiographic progression, a skeletal-related event, the initiation of new antineoplastic therapy, or death, whichever occurred first. The trial was designed to compare enzalutamide 160 mg once daily with bicalutamide 50 mg once daily, the approved dose in combination with an LHRH analogue.
The study achieved its primary endpoint, demonstrating a statistically significant increase in PFS for enzalutamide compared with bicalutamide (hazard ratio, 0.44; P < 0.0001). The median PFS was 15.7 months in the enzalutamide group compared with 5.8 months in the bicalutamide group. The median treatment periods were 11.7 months in the enzalutamide group and 5.8 months in the bicalutamide group.
Serious adverse events were reported in 31.1% of enzalutamide-treated patients and in 23.0% of bicalutamide-treated patients. Individual grade-3 or higher adverse events largely occurred at a similar rate between the two treatment groups, with the exception of hypertension (7.1% for enzalutamide versus 4.2% for bicalutamide) and back pain (2.7% versus 1.6%). Grade-3 or higher cardiac events were reported in 5.5% of enzalutamide-treated patients compared with 2.1% of bicalutamide-treated patients. Two seizures were reported in the enzalutamide group and one in the bicalutamide group. The most common adverse events associated with enzalutamide therapy included fatigue, back pain, hot flush, hypertension, diarrhea, decreased weight, and pain in an extremity.
Enzalutamide is an androgen receptor inhibitor that acts on multiple steps in the androgen receptor signaling pathway within tumor cells. In preclinical studies, enzalutamide was shown to competitively inhibit androgen binding to androgen receptors, and to inhibit androgen receptor nuclear translocation and interaction with DNA. The treatment is approved by the FDA for patients with metastatic castration-resistant prostate cancer.
Source: Astellas US; January 13, 2016.