Neal Shore, MD
Enzalutamide increased progression-free survival (PFS) by nearly 10 months compared with bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC). These topline results from the phase II TERRAIN trial were announced by Medivation, Inc. and Astellas Pharma Inc., the companies co-developing enzalutamide.
“There is a desire among healthcare professionals and payers to see head-to-head data between enzalutamide and bicalutamide,” Neal Shore, MD, co-principal investigator of the TERRAIN study and medical director, Carolina Urologic Research Center, said in an interview with OncLive
. “The results from TERRAIN may help inform how clinicians treat metastatic castration-resistant prostate cancer patients after they fail LHRH therapy or surgical castration.”
TERRAIN enrolled 375 patients with mCRPC whose disease progressed following treatment with an LHRH analogue or following surgical castration. Inclusion criteria for the study were metastatic disease (at least two bone lesions or soft tissue disease), progressive disease (at least three rising PSA levels or new bone/soft tissue disease), ongoing GnRH analog therapy or surgical castration, ECOG status of 0 or 1, and life expectancy of at least 1 year.
Exclusion criteria included patients who had previously received chemotherapy or current/prior antiandrogen therapy (except if administered for <12 weeks and discontinued at ≥6 months before trial).
The study was conducted at 46 sites in the United States and 32 locations internationally.2
Patients were randomized to 160 mg of enzalutamide or 50 mg of bicalutamide, each taken once daily. Shore noted that this was generally a second-line therapy for patients and was administered prior to chemotherapy.
The primary endpoint was PFS, defined as time from randomization to radiographic progression, skeletal related event, initiation of new antineoplastic therapy or death, whichever occurred first. Secondary endpoints focused on PSA response and time to PSA progression.1
Median PFS was 15.7 months in the enzalutamide arm compared with 5.8 months in the bicalutamide arm (HR = 0.44; 95% CI, 0.34-0.57; P
Median time on treatment was 11.7 months and 5.8 months in the enzalutamide and bicalutamide arms, respectively.
Adverse events between the two arms differed slightly. In total, 31.1% of patients treated with enzalutamide experienced serious adverse events, while 23.3% of patients who received bicalutamide experienced serious adverse events.
Incidence of grade 3 cardiac adverse events were 5.5% and 2.1% in the enzalutamide and bicalutamide arms, respectively. Diarrhea, fatigue, hot flush, hypertension, pain in extremities, and weight loss all occurred more frequently in the enzalutamide arm.
When asked about adverse events, including management, differing rates in the two arms, and rates of seizures, Shore reiterated several times that, “Full TERRAIN results, including secondary endpoint and safety data, are currently being analyzed.”
Three seizures in total were observed in the trial: two in the enzalutamide arm and one in the bicalutamide arm. The rates of seizures in this trial were similar to those observed in the PREVAIL trial, Shore noted, which compared enzalutamide with placebo in chemotherapy-naïve mCRPC.
Additional safety and secondary endpoint data will be submitted for presentation at a future medical conference, according to a press release.
“There are no plans to conduct a phase III study following completion of the TERRAIN trial,” Tyler Marciniak, director of oncology communications and advocacy at Astellas, said. “TERRAIN is a phase II trial with a composite endpoint and the impact of the trial data on regulatory strategy, if any, would only be discussed following review of the full data.”
Clincaltrials.gov. A Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer. Available at: https://clinicaltrials.gov/ct2/show/NCT01288911?term=mdv3100+bicalutamide&rank=1
Baskin-Bey ES, Shore ND, Barber K, et al. TERRAIN: A randomized, double-blind, phase II study comparing MDV3100 with bicalutamide (Bic) in men with metastatic castrate-resistant prostate cancer (CRPC). J Clin Oncol 30, 2012 (suppl; abstr TPS4698^)