Abstract
Purpose Dermatologic events (DEs) in patients with cancer treated with lapatinib, a small-molecule dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2), were characterized. Patients and methods Nine clinical trials of metastatic cancer were included in this analysis. Lapatinib was administered at doses ranging from 1000 to 1500 mg/day as monotherapy (n = 928) or in combination with paclitaxel or capecitabine (n = 491). Patients not treated with lapatinib comprised the control group. Dermatologic events included hand-foot syndrome, rash, hair disorder, dry skin, pruritus/urticaria, skin disorder, skin infection, and nail disorder; DEs were characterized based on type, time to onset, severity, duration, and required interventions. Results Fifty-eight percent of patients treated with lapatinib monotherapy, 74% treated with lapatinib plus paclitaxel or capecitabine, and 53% in the control group developed DEs. Among patients receiving lapatinib monotherapy, 55% experienced grade 1/2 DEs, 3% had grade 3 DEs, and no grade 4 DEs were observed. The most common DE was rash (43%); all other events occurred in ≤8% of patients. Most DEs developed between days 1 and 14 of starting treatment, with a median duration of 29 days. Three percent of DEs led to lapatinib dose reduction, 7% resulted in dose interruption, and 1% led to drug discontinuation. Conclusions Most DEs in lapatinib-treated patients present early, are mild to moderate in severity, and infrequently require dose modification or treatment interruption. Lapatinib-associated DEs appear to differ clinically from those associated with EGFR TKIs in both frequency and severity.
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Acknowledgments
We would like to thank the patients who enrolled in these studies, the medical personnel who cared for them, and Shradha Sainju from GlaxoSmithKline. We would also like to thank Jeff Riegel, PhD, and Ann Marie Fitzmaurice, PhD, ProEd Communications, Inc.® for their medical editorial assistance. Dr. Lacouture is supported by a Zell Scholarship from the Robert H Lurie Comprehensive Cancer Center of Northwestern University. GlaxoSmithKline conducted the clinical studies (i.e., funded, designed, and analyzed data) that were included in the pooled analysis of skin events associated with lapatinib treatment. GlaxoSmithKline also provided statistical support for the pooled analysis and medical writing support for manuscript development. M.E. Lacouture and M. Koehler were involved in the conception of the manuscript. A.J. Preston, M. Koehler, M.E. Lacouture, R. Sweetman, and K.L. Blackwell contributed to the design of the analysis. S.M. Laabs, V.M. Salazar, M. Koehler, R.W. Sweetman, A. Di Leo, and H.L. Gomez were involved in patient recruitment. M.E. Lacouture, S.M. Laabs, M. Koehler, R.W. Sweetman, A. Di Leo, V.M. Salazar, and K.M. Koch were involved in the collection and assembly of data and in data analysis and interpretation. As safety manager for lapatinib, J.A. Byrne contributed data and interpretation of side effects. M.E. Lacouture, S.M. Laabs, M. Koehler, V.M. Salazar, K.M. Koch, K.L. Blackwell, and J.A. Byrne contributed to manuscript development. All authors reviewed, revised, and approved the final draft of the manuscript.
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Lacouture, M.E., Laabs, S.M., Koehler, M. et al. Analysis of dermatologic events in patients with cancer treated with lapatinib. Breast Cancer Res Treat 114, 485–493 (2009). https://doi.org/10.1007/s10549-008-0020-7
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DOI: https://doi.org/10.1007/s10549-008-0020-7