Correspondence

Lapatinib plus Capecitabine in Breast Cancer

N Engl J Med 2007; 356:1471-1472April 5, 2007

Article

To the Editor:

In the trial reported by Geyer et al. (Dec. 28 issue),1 which compared capecitabine alone with a combination of lapatinib and capecitabine in women with HER2-positive advanced breast cancer, approximately 60% of patients had received trastuzumab within the previous 8 weeks. It is possible that the activity of lapatinib was enhanced by the persistence of trastuzumab levels in blood. Earlier studies of the pharmacokinetics of trastuzumab administered weekly or every 3 weeks indicate that the drug's half-life is 3 to 4 weeks, although this may be an underestimate. Therefore, synergism between lapatinib and trastuzumab, leading to a more complete blockade of the HER2 pathway, cannot be excluded and may partly account for the impressive improvement in outcomes with the combined regimen.

Guru Sonpavde, M.D.
U.S. Oncology Research, Houston, TX 77598
guru.sonpavde@usoncology.com

1 References

1. 1

   Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006;355:2733-2743
   Full Text | Web of Science | Medline

Author/Editor Response

We agree that many of the patients entering our trial probably had persistent levels of trastuzumab, which could have enhanced the activity of lapatinib. An exploratory analysis to determine whether the interval from the last dose of trastuzumab to randomization affected the activity of lapatinib was planned as a component of a subsequent updated analysis of the overall trial data. However, to provide a response to Sonpavde's question, we proceeded with an analysis of data from the 311 women who had received previous trastuzumab therapy and for whom the date of administration of the last dose had been reported (Table 1Table 1Effect of the Interval between the Administration of Trastuzumab and Randomization on Time to Disease Progression.). These results suggest that the contribution of residual trastuzumab to the activity of lapatinib was minimal.

Charles E. Geyer, M.D.
Allegheny General Hospital, Pittsburgh, PA 15212
cgeyer@wpahs.org

John Forster, M.Sc.
GlaxoSmithKline, Greenford UB6 0HE, United Kingdom

David Cameron, M.D.
Western General Hospital, Edinburgh EH4 2XU, United Kingdom

Citing Articles (5)

Citing Articles

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   Mohamed Chefrour, Gérard Milano, Patricia Formento, Sarah Giacometti, Amine Denden, Nicole Renée, Athanassios Iliadis, Jean-Louis Fischel, Joseph Ciccolini. (2011) Positive interaction between lapatinib and capecitabine in human breast cancer models: study of molecular determinants. Fundamental & Clinical Pharmacologyno-no
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2. 2

   Monica Giovannini, Daniela Aldrighetti, Patrizia Zucchinelli, Carmen Belli, Eugenio Villa. (2010) Antiangiogenic strategies in breast cancer management. Critical Reviews in Oncology/Hematology 76:1, 13-35
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   James E. Frampton. (2009) Lapatinib. Drugs 69:15, 2125-2148
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4. 4

   Gerald M. Higa. (2008) Targeting HER 1 and 2 in breast cancer with lapatinib. Oncology Reviews 2:1, 21-28
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5. 5

   Gerald M Higa, Jame Abraham. (2007) Lapatinib in the treatment of breast cancer. Expert Review of Anticancer Therapy 7:9, 1183-1192
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