SAN FRANCISCO — The addition of the mTOR inhibitor everolimus to exemestane therapy significantly improved PFS in patients with advanced ER-positive breast cancer, according to results of the phase 3 BOLERO-2 trial.
Treatment options for postmenopausal patients with ER-positive breast cancer who relapse or progress on a nonsteroidal aromatase inhibitor are limited, according to background information in the study.
“There has been intense interest in finding mechanisms to reverse the resistance to hormone therapy,” researcher Hope S. Rugo, MD, health sciences clinical professor at the University of California at San Francisco School of Medicine, said during a presentation. “About 80% of the patients we see have hormone receptor-positive breast cancer.”
In the international double blind study, Rugo and colleagues hypothesized that the addition of everolimus (Afinitor, Zortress) to therapy with the aromatase inhibitor exemestane (Aromasin, Pfizer) would prolong PFS in postmenopausal women with ER-positive breast cancer.
Rugo and colleagues randomly assigned 724 patients with a median age of 62 years to exemestane plus everolimus (n=485) or exemestane plus placebo (n=239).
Patients assigned to the combination therapy received exemestane 25 mg once daily and everolimus 10 mg once daily.
After 18 months of follow-up, median PFS among patients assigned to the combination therapy was 7.8 months compared with 3.2 months among patients who received exemestane alone (HR=0.43; P<.0001), Rugo said.
The response rate among patients assigned to the combination was 12.6% compared with 1.7% among those assigned to exemestane plus placebo.
At 12.5 months of follow-up, fewer deaths occurred in the combination arm (17.2% vs. 22.7%).
The analysis confirms previously reported benefits of everolimus, Rugo said during a press conference.
“The addition of everolimus to second-line steroidal aromatase inhibitor therapy with exemestane prolongs PFS in patients who have hormone receptor-positive breast cancer,” she said.
The percentage change in OS increased with each follow-up analysis; however, OS has yet to meet the endpoint for statistical significance.
At the time of data collection, researchers had observed 200 events. They intend to conduct an interim analysis once 275 events occur, and they will conduct the final analysis after 398 deaths occur.
For more information:
Arena FP. Abstract #99. Presented at: 2012 Breast Cancer Symposium; Sept. 13-15, 2012; San Francisco.
Disclosure: Researchers have received research funding and honoraria from, held employment or leadership roles with, or served as consultants or advisers for Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Merck, Novartis, Pfizer, Sanofi and other pharmaceutical companies.