SAN FRANCISCO — Postmenopausal women with ER-positive breast cancer who were treated with the mTOR inhibitor everolimus plus exemestane had significantly improved survival and bone metastases levels compared with patients assigned to exemestane alone, according to phase 3 results from the BOLERO-2 trial.
The multinational, double-blind, placebo-controlled study involved postmenopausal women with ER-positive breast cancer refractory to non-steroidal aromatase inhibitors (NSAIs).
Preclinical studies have shown mTOR inhibition was associated with decreased osteoclast survival and activity.
The current exploratory analysis served to evaluate the effects of everolimus on bone metastases and disease progression in patients with bone metastases at baseline.
All eligible participants were assigned exemestane 25 mg once daily. Patients then were randomly assigned to everolimus 10 mg daily (n=485) or placebo (n=239).
Exploratory endpoints included bone turnover markers at 6 and 12 weeks after initiation of treatment. Bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen served as the markers for analysis.
The researchers defined progressive disease in bone as worsening of a pre-existing bone lesion or a new bone lesion.
Bone metastases at baseline were similar between the two arms (76% of patients assigned to the study drug vs. 77% of patients assigned to placebo). However, bisphosphonate use at baseline was 44% among patients assigned to everolimus and 55% among those assigned to placebo.
After a median 12.5 months of follow-up, results indicated statistically superior results for everolimus compared with placebo in terms of PFS, overall response rate and clinical benefit rate (P<.0001 for all).
At 6 and 12 weeks, bone metastases levels increased vs. baseline for patients in the placebo group, but levels decreased vs. baseline for patients assigned to everolimus.
At day 60, the cumulative incidence rate of breast cancer progressive disease in bone was 3.03% among patients assigned to everolimus and 6.16% among patients assigned to placebo. This trend continued through the 6 month mark, according to researchers.
Adverse event profiles were comparable, with grade 1/grade 2 events occurring in 2.9% of patients assigned to everolimus and 3.8% of patients assigned to placebo.
For more information:
Hart LL. Abstract #102. Presented at: 2012 Breast Cancer Symposium; Sept. 13-15, 2012; San Francisco.
Disclosure: The researchers report serving as consultants/advisers for and receiving honoraria/research funding from Amgen, AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi and several other pharmaceutical companies.