Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy

Lung Cancer. 2007 Jun;56(3):383-9. doi: 10.1016/j.lungcan.2007.01.025. Epub 2007 Mar 26.


Purpose: Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of non-small cell lung cancer (NSCLC) to gefitinib, an EGFR tyrosine kinase inhibitor. The objective of this study was to prospectively evaluate the efficacy of gefitinib in patients with stage III/IV NSCLC whose tumors carried EGFR mutations, irrespective of previous chemotherapy.

Experimental design: Genomic DNA was extracted from tumor specimens and EGFR mutations in exons 19 and 21 analyzed by direct sequencing. Patients with stage III/IV NSCLC whose tumors had the EGFR mutations received gefitinib (250 mg/day orally). Response, toxicity and survival data were assessed.

Result: From November 2004-May 2006, 21 patients with EGFR mutations received gefitinib (median age: 59 years; 17 females; 19 non-smokers; all had adenocarcinomas). Two patients discontinued gefitinib and withdrew from the study 3 weeks after gefitinib initiation (interstitial pneumonitis, 1 patient; facial acne, 1 patient). Of 19 patients, 3 achieved complete response, 13 exhibited partial response and 3 had stable disease. Response and disease control rates were 76% (95% confidence interval [CI] 53-92) and 90% (95% CI 70-99), respectively. The most common adverse event was skin toxicity (67%); however, no grade 4 skin toxicities were seen. Ten patients relapsed and three died at a median follow-up period of 12.6 months (range 5.6-23.8 months); median progression-free survival was 12.9 months.

Conclusion: Analysis of tumor EGFR mutations in patients with NSCLC could be used to identify patients suitable for treatment with gefitinib to obtain optimum response and disease control rates.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • DNA, Neoplasm / genetics*
  • Disease Progression
  • Drug Administration Schedule
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Exons
  • Female
  • Follow-Up Studies
  • Gefitinib
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Prospective Studies
  • Quinazolines / administration & dosage
  • Quinazolines / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome


  • Antineoplastic Agents
  • DNA, Neoplasm
  • Quinazolines
  • ErbB Receptors
  • Gefitinib