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

Nancy U. Lin, Véronique Diéras, Devchand Paul, Dominique Lossignol, Christos Christodoulou, Hans Joachim Stemmler, Henri Roché, Minetta C. Liu, Richard Greil, Eva Ciruelos, Sibylle Loibl, Stefania Gori, Andrew Wardley, Denise Yardley, Adam Brufsky, Joanne L. Blum, Stephen D. Rubin, Bernie Dharan, Klaudia Steplewski, Denise ZembrykiCristina Oliva, Debasish Roychowdhury, Paolo Paoletti, Eric P. Winer

Research output: Contribution to journalArticlepeer-review

477 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1452-1459
Number of pages8
JournalClinical Cancer Research
Issue number4
StatePublished - Feb 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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