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

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. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.