results of phase II trial of lapatinib for her2+ brain mets (better with capecitabine

[Lani]

As that is the only FDA approved use, it is nice to know that there is more bang for the buck, so to say, with the combination
since adding Xeloda (capecitabine) certain seems to increase the incidence/severity of diarrhea and other GI symptoms compared to lapatinib alone

1: Clin Cancer Res. 2009 Feb 15;15(4):1452-1459.

Multicenter Phase II Study of Lapatinib in Patients with Brain Metastases from HER2-Positive Breast Cancer.

Lin NU, Diéras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, Roché H, Liu MC, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum JL, Rubin SD, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer EP.
Authors' Affiliations: Dana-Farber Cancer Institute, Boston Massachusetts, Institut Curie, Paris, France, Rocky Mountain Cancer Centers and U.S. Oncology, Denver, Colorado, Institut Jules Bordet, Brussels, Belgium, Metropolitan Hospital, Athens, Greece, Klinikum der Universität München, Munich, Germany, Institut Claudius Regaud, Toulouse, France, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, Private Medical University Hospital Salzburg, Salzburg, Austria, Hospital 12 De Octubre, Madrid, Spain, Klinikum der J.W. Goethe-Universitaet, Frankfurt, Germany, Azienda Opsedaliera di Perugia, Perugia, Italy, Christie Hospital NHS Foundation Trust, Manchester, United Kingdom, Sarah Cannon Cancer Center, Nashville, Tennessee, University of Pittsburgh, Magee Women's Hospital, Pittsburgh, Pennsylvania, Baylor-Sammons Cancer Center, Texas Oncology, U.S. Oncology Research, Dallas, Texas, GlaxoSmithKline, Upper Providence, Pennsylvania, and GlaxoSmithKline, Stockley Park, United Kingdom.
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.
PMID: 19228746