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

Journal Article (Journal Article;Multicenter Study)

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 approximately 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.

Full Text

Duke Authors

Cited Authors

  • Burstein, HJ; Storniolo, AM; Franco, S; Forster, J; Stein, S; Rubin, S; Salazar, VM; Blackwell, KL

Published Date

  • June 2008

Published In

Volume / Issue

  • 19 / 6

Start / End Page

  • 1068 - 1074

PubMed ID

  • 18283035

Electronic International Standard Serial Number (EISSN)

  • 1569-8041

Digital Object Identifier (DOI)

  • 10.1093/annonc/mdm601


  • eng

Conference Location

  • England