Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2

Abstract

Background: The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported.

Methods: Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety.

Results: Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients.

Conclusion: Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

Trial registration: ClinicalTrials.gov NCT00863655.

Fig. 1

CONSORT flowchart. ITT intention-to-treat. Ongoing treatment refers to those patients at time of cutoff for this analysis. Note that disease progression events in this figure are those that resulted in treatment discontinuation

Fig. 2

Kaplan–Meier analyses of progression-free survival in a Asian and b non-Asian patients with advanced breast cancer. CI confidence interval, EVE everolimus, EXE exemestane, HR hazard ratio, PBO placebo

Fig. 3

Forest plot of progression-free survival subgroup analysis by region and ethnicity. Subsets were prespecified in the analysis plan. Data from 18-months’ median follow-up. EVE everolimus, EXE exemestane, HR hazard ratio, PBO placebo, PFS progression-free survival

Fig. 4

Time to deterioration in EORTC QLQ-C30 (5 % decrease from baseline). CI confidence interval, EORTC QLQ-C30 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, EVE everolimus, EXE exemestane, PBO placebo, TTD time to definitive deterioration