Article (Scientific journals)
Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3.
Andre, Fabrice; Hurvitz, Sara; Fasolo, Angelica et al.
2016In Journal of Clinical Oncology, 34 (18), p. 2115-24
Peer Reviewed verified by ORBi
 

Files


Full Text
Molecular alterations and everolimus efficacy in human epidermal ....pdf
Publisher postprint (5.5 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
oncology
Abstract :
[en] PURPOSE: Two recent phase III trials, BOLERO-1 and BOLERO-3 (Breast Cancer Trials of Oral Everolimus), evaluated the addition of everolimus to trastuzumab and chemotherapy in human epidermal growth factor receptor 2-overexpressing advanced breast cancer. The current analysis aimed to identify biomarkers to predict the clinical efficacy of everolimus treatment. METHODS: Archival tumor samples from patients in BOLERO-1 and BOLERO-3 were analyzed using next-generation sequencing, immunohistochemistry, and Sanger sequencing. RESULTS: Biomarker data were available for 549 patients. PIK3CA activating mutations and PTEN loss were reported in 30% and 16% of BOLERO-1 samples and in 32% and 12% of BOLERO-3 samples, respectively. PI3K pathway was hyperactive (PIK3CA mutations and/or PTEN loss and/or AKT1 mutation) in 47% of BOLERO-1 and 41% of BOLERO-3 samples. In both studies, differential progression-free survival (PFS) benefits of everolimus were consistently observed in patient subgroups defined by their PI3K pathway status. When analyzing combined data sets of both studies, everolimus was associated with a decreased hazard of progression in patients with PIK3CA mutations (hazard ratio [HR], 0.67; 95% CI, 0.45 to 1.00), PTEN loss (HR, 0.54; 95% CI, 0.31 to 0.96), or hyperactive PI3K pathway (HR, 0.67; 95% CI, 0.48 to 0.93). Patients with wild-type PIK3CA (HR, 1.10; 95% CI, 0.83 to 1.46), normal PTEN (HR, 1.00; 95% CI, 0.80 to 1.26), or normal PI3K pathway activity (HR, 1.19; 95% CI, 0.87 to 1.62) did not derive PFS benefit from everolimus. CONCLUSION: This analysis, although exploratory, suggests that patients with human epidermal growth factor receptor 2-positive advanced breast cancer having tumors with PIK3CA mutations, PTEN loss, or hyperactive PI3K pathway could derive PFS benefit from everolimus.
Disciplines :
Oncology
Author, co-author :
Andre, Fabrice
Hurvitz, Sara
Fasolo, Angelica
Tseng, Ling-Ming
Jerusalem, Guy  ;  Université de Liège > Département des sciences cliniques > Oncologie
Wilks, Sharon
O'Regan, Ruth
Isaacs, Claudine
Toi, Masakazu
Burris, Howard
He, Wei
Robinson, Douglas
Riester, Markus
Taran, Tetiana
Chen, David
Slamon, Dennis
More authors (6 more) Less
Language :
English
Title :
Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3.
Publication date :
20 June 2016
Journal title :
Journal of Clinical Oncology
ISSN :
0732-183X
eISSN :
1527-7755
Publisher :
American Society of Clinical Oncology, United States - Virginia
Volume :
34
Issue :
18
Pages :
2115-24
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2016 by American Society of Clinical Oncology.
Available on ORBi :
since 22 June 2016

Statistics


Number of views
56 (3 by ULiège)
Number of downloads
0 (0 by ULiège)

Scopus citations®
 
135
Scopus citations®
without self-citations
123
OpenCitations
 
109

Bibliography


Similar publications



Contact ORBi