The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than 2-fold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.

BOLERO-2 is a phase 3, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO)+EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.

At the time of data cutoff (03 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE+EXE was 31.0 months (95% CI= 28.0-34.6 months) compared with 26.6 months (95% CI=22.6-33.1 months) in patients receiving PBO+EXE (hazard ratio=0.89; 95% CI=0.73-1.10; log-rank P=0.14). Post-study treatments were received by 84% of patients in the EVE+EXE arm versus 90% of patients in the PBO+EXE arm. Types of post-study therapies were balanced across arms, except for chemotherapy (53% EVE+EXE versus 63% PBO+EXE). No new safety concerns were identified.

In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P<0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.

NCT00863655.