Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations

J Clin Oncol. 2006 Jul 20;24(21):3340-6. doi: 10.1200/JCO.2005.05.4692. Epub 2006 Jun 19.

Abstract

Purpose: This study was undertaken to investigate the efficacy and the feasibility of gefitinib for chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.

Patients and methods: The EGFR gene status in various tumor samples obtained from chemotherapy-naïve advanced NSCLC patients was examined by DNA sequencing of EGFR exons 18 to 23. Patients harboring EGFR mutations received gefitinib (250 mg/d) alone. The response rate, progression-free survival (PFS), and toxicity profile were assessed prospectively.

Results: Between June 2004 and October 2005, 75 patients were examined for the EGFR status, and 25 patients (33%) harbored EGFR mutations. EGFR mutations were significantly frequent in females (P < .01) and never or light smokers (P < .001). Sixteen patients with EGFR mutations were enrolled onto the study. The overall response rate in these patients was 75% (95% CI, 54% to 96%), and the disease control rate was 88% (95% CI, 71% to 100%). The median PFS time of these patients was 9.7 months (95% CI, 7.4 to 9.9 months). No life-threatening toxicity was observed.

Conclusion: Treatment with gefitinib alone for chemotherapy-naïve NSCLC patients with EGFR mutations could achieve a high efficacy with acceptable toxicity. To assess the proper timing of gefitinib in such patients, a subsequent randomized trial comparing gefitinib with standard chemotherapy is warranted.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Arginine
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease-Free Survival
  • ErbB Receptors / genetics*
  • Feasibility Studies
  • Female
  • Gefitinib
  • Glutamic Acid
  • Humans
  • Leucine
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Positron-Emission Tomography
  • Prospective Studies
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Glutamic Acid
  • Arginine
  • ErbB Receptors
  • Leucine
  • Alanine
  • Gefitinib