A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses

Purpose Lapatinib 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. Methods Women 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. Results 399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43–0.77; P