• David Cameron, Michelle Casey, Michael Press, Deborah Lindquist, Tadeusz Pienkowski, C Gilles Romieu, Stephen Chan, Agnieszka Jagiello-Gruszfeld, Bella Kaufman, John Crown, Arlene Chan, Mario Campone, Patrice Viens, Neville Davidson, Vera Gorbounova, Johannes Isaac Raats, Dimosthenis Skarlos, Beth Newstat, Debasish Roychowdhury, Paolo Paoletti, Cristina Oliva, Stephen Rubin, Steven Stein, and Charles E Geyer.
• University of Leeds, Leeds, England, UK. d.cameron@ncrn.org.uk
• Breast Cancer Res. Treat. 2008 Dec 1; 112 (3): 533-43.

PurposeLapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported.MethodsWomen with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m(2) days 1-14 of a 21-day cycle or capecitabine 2,500 mg/m(2) on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed.Results399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43-0.77; P < 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55-1.12, P = 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13, P = 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib.ConclusionThe addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.

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