At the preplanned interim analysis, performed by an independent data and safety monitoring committee after 359 PFS events were observed, median PFS was 6.9 months in the everolimus plus exemestane arm (n=485) vs 2.8 months in the exemestane plus placebo arm (n=239), according to assessments by local investigators (HR for progression or death, 0.43 [95% CI, 0.35–0.54; P<0.001). By central assessment, median PFS was 10.6 months and 4.1 months, respectively (HR 0.36 [95% CI, 0.27–0.47; P<0.001).
The most common grade 3 or 4 adverse events (AEs) that occurred more frequently in the everolimus plus exemestane group vs the placebo group were stomatitis (8% vs 1%, respectively), anemia (6% vs <1%), dyspnea, 4% vs 1%, hyperglycemia (4% vs <1%), fatigue (4% vs 1%), and pneumonitis (3% vs 0%).
Long-Term PFS Reported
Results of the final, protocol-defined PFS data from the BOLERO-2 trial2 were presented at ASCO 2012 by Martine J. Piccart-Gebhart, MD, PhD, of the Jules Bordet Institute, Brussels, Belgium, and colleagues. After 528 events and a median follow-up of 18 months, analyses confirmed the benefits of everolimus plus exemestane reported at 7.5-month and 12.5-month follow-up when compared with placebo plus exemestane.
The primary efficacy analysis, based on local radiologic assessment, resulted in an estimated 55% risk reduction for PFS (HR 0.45 [95% CI, 0.38–0.54; P<0.0001), which corresponded to a clinically meaningful 4.6-month prolongation in median PFS, from 3.2 months in the placebo plus exemestane arm to 7.8 months in the everolimus plus exemestane arm.
When PFS was analyzed based on central radiologic assessment, an estimated 62% risk reduction of progression or death was observed for the everolimus plus exemestane arm vs the placebo plus exemestane arm (HR 0.38 [95% CI, 0.31–0.48]; P<0.0001), which corresponded to a clinically meaningful 6.9-month prolongation in median PFS, from 4.1 months in the placebo plus exemestane arm to 11.0 months in the everolimus plus exemestane arm.
By local assessment, ORR was significantly higher in the everolimus plus exemestane arm vs the placebo plus exemestane arm; 12.6% vs 1.7% (P<0.0001), as was clinical benefit rate, 51.3% vs 26.4% (P<0.0001), respectively, with similar results observed by central assessment.
The most common grade 3 or 4 AEs were stomatitis, hyperglycemia, and fatigue. The AEs observed with everolimus plus exemestane are consistent with previous reports for mTOR inhibitors.10
At the cut-off date of December 15, 2011, 16.7% of patients in the everolimus plus exemestane arm and 4.2% in the placebo plus exemestane arm continued to receive study treatment. The primary reason for treatment discontinuation was disease progression. A higher percentage of patients in the everolimus plus exemestane arm (9.1%) discontinued treatment due to AEs when compared with the placebo plus exemestane arm (3.3%); a greater percentage in the combination arm also withdrew consent, 9.5% vs 2.9%, respectively. Higher discontinuation rates among patients treated with everolimus may be attributable to the longer treatment duration in the combination arm.
A total of 200 deaths had occurred at the cut-off date, 25.4% in the everolimus plus exemestane arm and 32.2% in the placebo plus exemestane arm. The next interim analysis of survival will be performed after 275 deaths occur, with final OS analysis conducted after 398 deaths.
These results support the use of everolimus-based endocrine therapy combinations in postmenopausal women with advanced ER+ breast cancer, Dr. Piccart-Gebhart reported.