TY - JOUR
T1 - Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer
AU - Lin, Nancy U.
AU - Diéras, Véronique
AU - Paul, Devchand
AU - Lossignol, Dominique
AU - Christodoulou, Christos
AU - Stemmler, Hans Joachim
AU - Roché, Henri
AU - Liu, Minetta C.
AU - Greil, Richard
AU - Ciruelos, Eva
AU - Loibl, Sibylle
AU - Gori, Stefania
AU - Wardley, Andrew
AU - Yardley, Denise
AU - Brufsky, Adam
AU - Blum, Joanne L.
AU - Rubin, Stephen D.
AU - Dharan, Bernie
AU - Steplewski, Klaudia
AU - Zembryki, Denise
AU - Oliva, Cristina
AU - Roychowdhury, Debasish
AU - Paoletti, Paolo
AU - Winer, Eric P.
PY - 2009/2/15
Y1 - 2009/2/15
N2 - 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 ≥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 ≥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 ≥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.
AB - 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 ≥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 ≥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 ≥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.
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U2 - 10.1158/1078-0432.CCR-08-1080
DO - 10.1158/1078-0432.CCR-08-1080
M3 - Article
C2 - 19228746
AN - SCOPUS:63149110733
SN - 1078-0432
VL - 15
SP - 1452
EP - 1459
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -