Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC

J Clin Oncol. 2003 Jul 15;21(14):2658-63. doi: 10.1200/JCO.2003.01.039.

Abstract

Purpose: To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time.

Patients and methods: Patients with pretreated advanced non-small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry.

Results: From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P =.126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2

Conclusion: According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Confidence Intervals
  • Disease Progression
  • Dose-Response Relationship, Drug
  • ErbB Receptors / analysis
  • ErbB Receptors / metabolism*
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Preoperative Care / methods
  • Probability
  • Prognosis
  • Prospective Studies
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / metabolism*
  • Risk Assessment
  • Sensitivity and Specificity
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Quinazolines
  • ErbB Receptors
  • Receptor, ErbB-2
  • Gefitinib