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Clinical Trial
. 2014 Dec;25(12):2357-2362.
doi: 10.1093/annonc/mdu456. Epub 2014 Sep 17.

Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†

M Piccart  1 , G N Hortobagyi  2 , M Campone  3 , K I Pritchard  4 , F Lebrun  5 , Y Ito  6 , S Noguchi  7 , A Perez  8 , H S Rugo  9 , I Deleu  10 , H A Burris 3rd  11 , L Provencher  12 , P Neven  13 , M Gnant  14 , M Shtivelband  15 , C Wu  16 , J Fan  16 , W Feng  16 , T Taran  16 , J Baselga  17
Affiliations
Clinical Trial

Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†

M Piccart et al. Ann Oncol. 2014 Dec.

Abstract

Background: The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold 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.

Patients and methods: BOLERO-2 is a phase III, 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.

Results: At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (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). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.

Conclusions: 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.

Trial registration number: NCT00863655.

Keywords: everolimus; exemestane; hormone-receptor-positive breast cancer; overall survival.

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Figures

Figure 1.
Figure 1.
Kaplan–Meier estimates of overall survival. CI, confidence interval; EVE, everolimus; EXE, exemestane; HR, hazard ratio; PBO, placebo.
See this image and copyright information in PMC

References

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