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Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer.

Lin, Nancy U
; 
Diéras, Véronique
; 
Paul, Devchand
; 
Lossignol, Dominique
; 
Christodoulou, Christos
; 
Stemmler, Hans-Joachim
; 
Roché, Henri
; 
Liu, Minetta C
; 
Greil, Richard
; 
Ciruelos, Eva
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Abstract
PURPOSE: Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial. The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine. EXPERIMENTAL DESIGN: Eligible patients had HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy. The primary end point was CNS objective response, defined as >or=50% volumetric reduction of CNS lesion(s) in the absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease. RESULTS: Two-hundred and forty-two patients entered the study. CNS objective responses to lapatinib were observed in 6% of patients. In an exploratory analysis, 21% of patients experienced a >or=20% volumetric reduction in their CNS lesions. An association was observed between volumetric reduction and improvement in progression-free survival and neurologic signs and symptoms. Of the 50 evaluable patients who entered the lapatinib plus capecitabine extension, 20% experienced a CNS objective response and 40% experienced a >or=20% volumetric reduction in their CNS lesions. CONCLUSIONS: This study confirms the modest CNS antitumor activity of lapatinib. Additional responses were observed with the combination of lapatinib and capecitabine. Further studies of lapatinib-based regimens for CNS metastases from HER2+ breast cancer are warranted.
Authors
Lin, Nancy U
Diéras, Véronique
Paul, Devchand
Lossignol, Dominique
Christodoulou, Christos
Stemmler, Hans-Joachim
Roché, Henri
Liu, Minetta C
Greil, Richard
Ciruelos, Eva
Loibl, Sibylle
Gori, Stefania
Wardley, Andrew M
Yardley, Denise
Brufsky, Adam
Blum, Joanne L
Rubin, Stephen D
Dharan, Bernie
Steplewski, Klaudia
Zembryki, Denise
Oliva, Cristina
Roychowdhury, Debasish F
Paoletti, Paolo
Winer, Eric P
Affiliation
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Description
Date
2009-02-15
Publisher
Collections
All Christie Publications
Medical Oncology
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Keywords
Breast Cancer
Brain Cancer
Brain Tumour
Type
Article
Citation
Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. 2009, 15 (4):1452-9 Clin. Cancer Res.
Journal Title
Journal ISSN
Volume Title
URI
http://hdl.handle.net/10541/69595
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