A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer

H. J. Burstein, Anna Maria Storniolo, S. Franco, J. Forster, S. Stein, S. Rubin, V. M. Salazar, K. L. Blackwell

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Abstract

Background: The efficacy and tolerability of the epidermal growth factor receptor/human epidermal growth factor receptor type 2 (HER2) tyrosine kinase inhibitor lapatinib in refractory metastatic breast cancer were assessed. Patients and methods: In a phase II, open-label study, patients with previously treated HER2-positive (n = 140) or HER2-negative (n = 89) metastatic breast cancer received once-daily oral lapatinib 1500 mg/day. Results: Most (76%) patients had received four or more lines of prior therapy. The response rate in the HER2-positive cohort was 4.3% by investigator assessment and 1.4% by independent assessment. Both assessments established that ∼6% of HER2-positive patients derived clinical benefit from lapatinib, being progression free for ≥6 months. No objective tumor responses occurred in the HER2-negative cohort. Independent review assessments of median time to progression and median progression-free survival were similar in the HER2-positive and HER2-negative cohorts (9.1 and 7.6 weeks, respectively). All responders exhibited HER2 overexpression (3+ by immunohistochemistry), and five of six responders were HER2 amplified by FISH. Lapatinib-related adverse events, including diarrhea (54%), rash (30%), and nausea (24%), were primarily mild to moderate in severity. Conclusions: Lapatinib monotherapy had modest clinical activity in HER2-positive metastatic breast cancer that progressed on prior trastuzumab regimens. No apparent clinical activity was observed in chemotherapy-refractory, HER2-negative disease.

Original languageEnglish
Pages (from-to)1068-1074
Number of pages7
JournalAnnals of Oncology
Volume19
Issue number6
DOIs
StatePublished - Jun 2008

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Breast Neoplasms
Drug Therapy
Exanthema
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Nausea
Disease-Free Survival
Diarrhea
Immunohistochemistry
Research Personnel
lapatinib
Neoplasms
Therapeutics

Keywords

  • Breast cancer
  • EGFR
  • ErbB2
  • Targeted therapy
  • Trastuzumab
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. / Burstein, H. J.; Storniolo, Anna Maria; Franco, S.; Forster, J.; Stein, S.; Rubin, S.; Salazar, V. M.; Blackwell, K. L.

In: Annals of Oncology, Vol. 19, No. 6, 06.2008, p. 1068-1074.

Research output: Contribution to journalArticle

Burstein, H. J. ; Storniolo, Anna Maria ; Franco, S. ; Forster, J. ; Stein, S. ; Rubin, S. ; Salazar, V. M. ; Blackwell, K. L. / A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. In: Annals of Oncology. 2008 ; Vol. 19, No. 6. pp. 1068-1074.
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AU - Forster, J.

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