The results from the phase 2 TERRAIN trial of Enzalutamide ( Xtandi ) compared to Bicalutamide ( Casodex ) in metastatic castration-resistant prostate cancer ( CRPC ) are published in the Lancet Oncology.
The TERRAIN study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival ( PFS ) for Enzalutamide compared to Bicalutamide ( hazard ratio, HR=0.44; 95% Confidence Interval, 0.34-0.57; p less than 0.0001 ).
Median progression-free survival, defined as time from randomization to centrally confirmed radiographic progression, skeletal-related event, initiation of new anti-neoplastic therapy or death, whichever occurred first, was 15.7 months in the Enzalutamide group compared to 5.8 months in the Bicalutamide group.
The observed adverse event profile of Enzalutamide in TERRAIN appeared consistent with that from phase 3 Enzalutamide trials.
TERRAIN is the first and largest head-to-head trial comparing Enzalutamide with Bicalutamide that evaluated both the efficacy and safety of these agents in the treatment of men with metastatic castration-resistant prostate cancer.
The median time on treatment in TERRAIN was 11.7 months in the Enzalutamide group versus 5.8 months in the Bicalutamide group.
Serious adverse events were reported in 31.1% of Enzalutamide-treated patients and 23% of Bicalutamide-treated patients. Individual grade 3 or higher adverse events largely occurred at a similar rate ( less than 1% difference ) between treatment groups, with the exception of hypertension ( 7.1% vs 4.2% ) and back pain ( 2.7% vs. 1.6% ), which occurred more frequently in the Enzalutamide treatment group.
Grade 3 or higher cardiac events were reported in 5.5% of Enzalutamide-treated patients versus 2.1% of Bicalutamide-treated patients.
Two seizures were reported in the Enzalutamide group and one in the Bicalutamide group.
The most common side effects occurring during treatment and more common in the Enzalutamide-treated versus Bicalutamide-treated patients included fatigue, back pain, hot flush, hypertension, diarrhea, weight decreased and pain in extremity.
The phase 2 TERRAIN trial enrolled 375 patients in North America and Europe. The trial enrolled patients with metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone ( LHRH ) analogue therapy or following surgical castration.
The primary endpoint of the trial was progression-free survival, defined as time from randomization to centrally confirmed radiographic progression, skeletal-related event, initiation of new anti-neoplastic therapy or death, whichever occurred first.
The trial was designed to evaluate Enzalutamide at a dose of 160 mg taken orally once daily versus Bicalutamide at a dose of 50 mg taken once daily, the approved dose in combination with an LHRH analogue.
Enzalutamide is an androgen receptor inhibitor that acts on multiple steps in the androgen receptor signaling pathway within the tumor cell.
In preclinical studies, Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and inhibit androgen receptor nuclear translocation and interaction with DNA. ( Xagena )
Source: Astellas, 2016