Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: Subgroup analysis from the BOLERO-2 study

Mario Campone, Thomas Bachelot, Michael Gnant, Ines Deleu, Hope S. Rugo, Barbara Pistilli, Shinzaburo Noguchi, Mikhail Shtivelband, Kathleen I. Pritchard, Louise Provencher, Howard A. Burris, Lowell Hart, Bohuslav Melichar, Gabriel N. Hortobagyi, Francis Arena, José Baselga, Ashok Panneerselvam, Aurelia Héniquez, Mona El-Hashimyt, Tetiana TaranTarek Sahmoud, Martine Piccart

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55 Citations (Scopus)

Abstract

Background Everolimus (EVE; an inhibitor of mammalian target of rapamycin [mTOR]) enhances treatment options for postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) who progress on a non-steroidal aromatase inhibitor (NSAI). This is especially true for patients with visceral disease, which is associated with poor prognosis. The BOLERO-2 (Breast cancer trial of OraL EveROlimus-2) trial showed that combination treatment with EVE and exemestane (EXE) versus placebo (PBO) + EXE prolonged progression-free survival (PFS) by both investigator (7.8 versus 3.2 months, respectively) and independent (11.0 versus 4.1 months, respectively) central assessment in postmenopausal women with HR+, HER2- ABC recurring/progressing during/after NSAI therapy. The BOLERO-2 trial included a substantial proportion of patients with visceral metastases (56%). Methods Prespecified exploratory subgroup analysis conducted to evaluate the efficacy and safety of EVE + EXE versus PBO + EXE in a prospectively defined subgroup of patients with visceral metastases. Findings At a median follow-up of 18 months, EVE + EXE significantly prolonged median PFS compared with PBO + EXE both in patients with visceral metastases (N = 406; 6.8 versus 2.8 months) and in those without visceral metastases (N = 318; 9.9 versus 4.2 months). Improvements in PFS with EVE + EXE versus PBO + EXE were also observed in patients with visceral metastases regardless of Eastern Cooperative Oncology Group performance status (ECOG PS). Patients with visceral metastases and ECOG PS 0 had a median PFS of 6.8 months with EVE + EXE versus 2.8 months with PBO + EXE. Among patients with visceral metastases and ECOG PS ≥1, EVE + EXE treatment more than tripled median PFS compared with PBO + EXE (6.8 versus 1.5 months). Interpretation Adding EVE to EXE markedly extended PFS by ≥4 months among patients with HR+ HER2- ABC regardless of the presence of visceral metastases. Funding Novartis.

Original languageEnglish
Pages (from-to)2621-2632
Number of pages12
JournalEuropean Journal of Cancer
Volume49
Issue number12
DOIs
Publication statusPublished - 1 Aug 2013
Externally publishedYes

Keywords

  • Advanced breast cancer
  • Everolimus
  • Exemestane
  • Visceral metastases

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