Safety and Efficacy of Everolimus With Exemestane vs. Exemestane Alone in Elderly Patients With HER2-Negative, Hormone Receptor-Positive Breast Cancer in BOLERO-2

The paucity of randomized breast cancer trials in elderly patients limits the data available for optimal treatment selection in this patient population, especially in elderly patients with comorbidities and increased susceptibility to adverse events. In the BOLERO-2 (Breast Cancer Trials of Oral Everolimus-2) phase III trial (N [724) everolimus (EVE) plus exemestane (EXE) provided substantial clinical benefit in elderly patients with hormone receptorepositive (HR+) advanced breast cancer and was generally well tolerated. Background: Postmenopausal women with hormone receptorepositive (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. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.