Article (Scientific journals)
Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial.
Andre, Fabrice; O'Regan, Ruth; Ozguroglu, Mustafa et al.
2014In The Lancet Oncology
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Keywords :
oncology
Abstract :
[en] BACKGROUND: Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapy. Eligible patients were randomly assigned (1:1) using a central patient screening and randomisation system to daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m2) or to placebo plus trastuzumab plus vinorelbine, in 3-week cycles, stratified by previous lapatinib use. The primary endpoint was progression-free survival (PFS) by local assessment in the intention-to-treat population. We report the final analysis for PFS; overall survival follow-up is still in progress. This trial is registered with ClinicalTrials.gov, number NCT01007942. FINDINGS: Between Oct 26, 2009, and May 23, 2012, 569 patients were randomly assigned to everolimus (n=284) or placebo (n=285). Median follow-up at the time of analysis was 20.2 months (IQR 15.0-27.1). Median PFS was 7.00 months (95% CI 6.74-8.18) with everolimus and 5.78 months (5.49-6.90) with placebo (hazard ratio 0.78 [95% CI 0.65-0.95]; p=0.0067). The most common grade 3-4 adverse events were neutropenia (204 [73%] of 280 patients in the everolimus group vs 175 [62%] of 282 patients in the placebo group), leucopenia (106 [38%] vs 82 [29%]), anaemia (53 [19%] vs 17 [6%]), febrile neutropenia (44 [16%] vs ten [4%]), stomatitis (37 [13%] vs four [1%]), and fatigue (34 [12%] vs 11 [4%]). Serious adverse events were reported in 117 (42%) patients in the everolimus group and 55 (20%) in the placebo group; two on-treatment deaths due to adverse events occurred in each group. INTERPRETATION: The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated, HER2-positive, advanced breast cancer. The clinical benefit should be considered in the context of the adverse event profile in this population. FUNDING: Novartis Pharmaceuticals Corporation.
Disciplines :
Oncology
Author, co-author :
Andre, Fabrice
O'Regan, Ruth
Ozguroglu, Mustafa
Toi, Masakazu
Xu, Binghe
Jerusalem, Guy  ;  Université de Liège - ULiège > Département des sciences cliniques > Oncologie
Masuda, Norikazu
Wilks, Sharon
Arena, Francis
Isaacs, Claudine
Yap, Yoon-Sim
Papai, Zsuzsanna
Lang, Istvan
Armstrong, Anne
Lerzo, Guillermo
White, Michelle
Shen, Kunwei
Litton, Jennifer
Chen, David
Zhang, Yufen
Ali, Shyanne
Taran, Tetiana
Gianni, Luca
More authors (13 more) Less
Language :
English
Title :
Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial.
Publication date :
2014
Journal title :
The Lancet Oncology
ISSN :
1470-2045
eISSN :
1474-5488
Publisher :
The Lancet Publishing Group, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Elsevier Ltd. All rights reserved.
Available on ORBi :
since 08 May 2014

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