Southwest Oncology Group study S0413: A phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer

S. Iqbal, B. Goldman, C. M. Fenoglio-Preiser, H. J. Lenz, W. Zhang, K. D. Danenberg, S. I. Shibata, C. D. Blanke

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Background: Lapatinib (GW572016) is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/ErbB2), which are reported as overexpressed in 15%-45% of gastric cancers, making them potential targets. Patients and methods: The primary objective of this study was to assess response rate. Secondary objectives included overall survival (OS), toxicity, and the relationship of EGFR, ErbB2, and markers of angiogenesis with clinical outcome. Lapatinib was administered to chemonaive metastatic gastric cancer patients at a dose of 1500 mg orally daily for 28 days. Results: The study enrolled 47 patients from February 2005 until May 2006. Four patients (9%) had a confirmed partial response (PR), 1 (2%) had an unconfirmed PR, and 10 (23%) had stable disease. Median (95% confidence interval) time to treatment failure was 1.9 (1.6-3.1) months and OS was 4.8 (3.2-7.4) months. Significant adverse events: one grade 4 cardiac ischemia/infarction, one grade 4 fatigue, and one grade 4 emesis. One treatment-related death was due to central nervous system ischemia. An exploratory analysis of markers revealed gene expression of HER2, interleukin (IL)-8 and genomic polymorphisms IL-8, and vascular endothelial growth factor correlated with OS. Conclusions: Lapatinib is well tolerated, with modest single-agent activity in advanced/metastatic gastric cancer patients. Potential molecular correlatives were identified which warrant further validation.

Original languageEnglish (US)
Pages (from-to)2610-2615
Number of pages6
JournalAnnals of Oncology
Volume22
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • EGFR
  • Gastric cancer
  • HER2
  • Lapatinib

ASJC Scopus subject areas

  • Hematology
  • Oncology

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