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 3rd, Lowell Hart, Bohuslav Melichar, Gabriel N Hortobagyi, Francis Arena, José Baselga, Ashok Panneerselvam, Aurelia Héniquez, Mona El-Hashimyt, Tetiana Taran, Tarek Sahmoud, Martine Piccart, 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 3rd, Lowell Hart, Bohuslav Melichar, Gabriel N Hortobagyi, Francis Arena, José Baselga, Ashok Panneerselvam, Aurelia Héniquez, Mona El-Hashimyt, Tetiana Taran, Tarek Sahmoud, Martine Piccart
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 OraLEveROlimus-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.
Keywords: Advanced breast cancer; Everolimus; Exemestane; Visceral metastases.
Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed