Lapatinib plus capecitabine for HER2-positive advanced breast cancer

Charles E. Geyer, John Forster, Deborah Lindquist, Stephen Chan, C. Gilles Romieu, Tadeusz Pienkowski, Agnieszka Jagiello-Gruszfeld, John Crown, Arlene Chan, Bella Kaufman, Dimosthenis Skarlos, Mario Campone, Neville Davidson, Mark Berger, Cristina Oliva, Stephen D. Rubin, Steven Stein, David Cameron

Research output: Contribution to journalArticlepeer-review

2504 Scopus citations

Abstract

BACKGROUND: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2, also referred to as HER2/neu) and epidermal growth factor receptor (EGFR), is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy. In this trial, we compared lapatinib plus capecitabine with capecitabine alone in such patients. METHODS: Women with HER2-positive, locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab were randomly assigned to receive either combination therapy (lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle) or monotherapy (capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle). The primary end point was time to progression, based on an evaluation by independent reviewers under blinded conditions. RESULTS: The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events. CONCLUSIONS: Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab.

Original languageEnglish (US)
Pages (from-to)2733-2743
Number of pages11
JournalNew England Journal of Medicine
Volume355
Issue number26
DOIs
StatePublished - Dec 28 2006

ASJC Scopus subject areas

  • Medicine(all)

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