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

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 PaolettiCristina Oliva, Stephen Rubin, Steven Stein, Charles E. Geyer

Research output: Contribution to journalArticle

610 Scopus citations

Abstract

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/m2 days 1-14 of a 21-day cycle or capecitabine 2,500 mg/m2 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 < 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. Conclusion: The 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.

Original languageEnglish (US)
Pages (from-to)533-543
Number of pages11
JournalBreast Cancer Research and Treatment
Volume112
Issue number3
DOIs
StatePublished - Dec 2008

Keywords

  • Advanced breast cancer
  • Biomarker
  • Capecitabine
  • Dual tyrosine kinase inhibitor
  • HER2-positive
  • Lapatinib
  • Metastatic breast cancer
  • Phase III

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cameron, D., Casey, M., Press, M., Lindquist, D., Pienkowski, T., Romieu, C. G., Chan, S., Jagiello-Gruszfeld, A., Kaufman, B., Crown, J., Chan, A., Campone, M., Viens, P., Davidson, N., Gorbounova, V., Raats, J. I., Skarlos, D., Newstat, B., Roychowdhury, D., ... Geyer, C. E. (2008). 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. Breast Cancer Research and Treatment, 112(3), 533-543. https://doi.org/10.1007/s10549-007-9885-0