Chicago, IL—The novel androgen receptor–signaling inhibitor enzalutamide, also known as MDV3100, significantly prolonged overall survival (OS), slowed disease progression, and improved quality-of-life (QOL) measures in men with castration-resistant prostate cancer after docetaxel failure, according to results from a large phase 3 clinical trial.
In this double-blind, randomized trial, OS improved from 13.6 months in the placebo group to 18.4 months in the enzalutamide group, for a 37% reduction in the risk of death, said Johann S. de Bono, MB, ChB, MSc, PhD, of the Institute of Cancer Research and the Royal Mardsen National Health Service Foundation Trust, United Kingdom, at the 2012 American Society of Clinical Oncology meeting.
“I think these are the best survival data we’ve seen in the postchemotherapy setting,” Dr de Bono said.
A total of 1199 patients with castration-resistant prostate cancer who had received docetaxel-based chemotherapy were randomized in a 2:1 ratio to daily enzalutamide or to placebo. Therapy was continued through minor changes in prostate-specific antigen (PSA) level. Treatment with glucocorticoids was allowed but not required.
More than 25% of patients had softtissue disease involving the liver or the lung. More than 90% of patients had bone metastases. Approximately 50% of the patients in each arm had ≥3 previous lines of hormonal drug therapy.
The trial was unblinded early after the Independent Data Monitoring Committee determined that the risk-to-benefit ratio with MDV3100 was favorable; eligible patients in the placebo arm were offered treatment with enzalutamide.
With a median follow-up of 14.4 months, enzalutamide conferred a survival advantage across all identified subgroups.
“Impressively, enzalutamide had a very high PSA response rate,” said Dr de Bono. With enzalutamide, 25% of patients had a >90% fall in PSA level compared with only 1% with placebo.
“I never thought I’d see a 50% and 90% fall in PSA in this population of patients, with 54% of patients having a more than 50% confirmed PSA fall,” Dr de Bono said.
All of the secondary end points in the study favored the treatment arm. PSA progression-free survival (PFS) was extended from 3.0 months in the placebo group to 8.3 months in the enzalutamide group. Similarly, the radiographic PFS was 2.9 months in the placebo group and 8.3 months in the enzalutamide group, for a hazard ratio of 0.40 in favor of enzalutamide.
Objective response rates (complete and partial) based on the Response Evaluation Criteria in Solid Tumors (RECIST) trial were 3.8% in the placebo arm and 28.9% in the enzalutamide arm.
The time to a first skeletal event was again superior in the enzalutamide arm (16.7 months) compared with the placebo arm (13.3 months)—a 38% reduction in the risk of a skeletal-related event.
QOL responses as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) were also superior with enzalutamide. In that group, 43.2% had at least a 10-point increase in the overall FACT-P score compared with 18.3% in the placebo group.
A smaller proportion of patients treated with enzalutamide had grade ≥3 adverse events (AEs) compared with placebo (45.3% vs 53.1%, respectively). Serious AEs also occurred at a lower rate with enzalutamide than placebo (28.4% vs 33.6%). Seizure rates were 0.6% with enzalutamide and 0% with placebo.
