Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2

Clin Breast Cancer. 2013 Dec;13(6):421-432.e8. doi: 10.1016/j.clbc.2013.08.011.

Abstract

Background: Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest.

Patients and methods: BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up.

Results: Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths.

Conclusion: Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population.

Keywords: Advanced breast cancer; Endocrine resistance; Geriatric; Progression-free survival; Safety.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstadienes / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Everolimus
  • Female
  • Follow-Up Studies
  • Humans
  • International Agencies
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Safety
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives
  • Survival Rate

Substances

  • Androstadienes
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Everolimus
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • exemestane
  • Sirolimus