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Lung Cancer

Good Response to Gefitinib in Lung Adenocarcinoma of Complex Epidermal Growth Factor Receptor (EGFR) Mutations with the Classical Mutation Pattern

^aDepartment of Internal Medicine, ^bDepartment of Pathology, and ^cDepartment of Oncology, National Taiwan University Hospital, Taipei, Taiwan; ^dDepartment of Molecular Biotechnology, Da-Yeh University, Chang-Hua, Taiwan

Key Words. EGFR mutation • Gefitinib • Lung cancer • EGFR TKI • Complex mutation pattern

Correspondence: Jin-Yuan Shih, M.D. Ph.D., Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. Telephone: 886-2-23562905; Fax: 886-2-23582867; e-mail: jyshih{at}ntu.edu.tw

Received April 14, 2008; accepted for publication November 10, 2008; first published online in THE ONCOLOGIST Express on December 5, 2008.

Disclosure: Employment/leadership position: None; Intellectual property rights/inventor/patent holder: None; Consultant/advisory role: Chih-Hsin Yang, AstraZeneca; Honoraria: None; Research funding/contracted research: None; Ownership interest: None; Expert testimony: None; Other: None.

Background. Epidermal growth factor receptor (EGFR) mutations are usually detected in lung adenocarcinoma and are associated with a response to EGFR tyrosine kinase inhibitors (TKIs). However, not all EGFR mutations have similarly high clinical response rates. This study aimed to investigate the clinical characteristics and response to gefitinib in lung adenocarcinoma patients with complex EGFR mutations.

Materials and Methods. Three hundred thirty-nine specimens of lung adenocarcinoma from patients treated with gefitinib were collected for EGFR sequencing. Nineteen patients with complex EGFR mutations were enrolled for the study after excluding three patients with the EGFR T790M mutation, which confers resistance to gefitinib.

Results. Among the 19 patients, 12 had complex mutations with the classical mutation pattern (L858R or deletion in exon 19). When compared with those without the classical mutation pattern, patients with this mutation pattern had a higher response rate (83% versus 29%), longer progression-free survival duration (median, 12.7 months versus 4.9 months), and longer overall survival time (median, 24.7 months versus 12.3 months) after gefitinib treatment.

Comparing patients harboring complex EGFR mutations with a classical mutation pattern with those harboring single classical mutations, there were no statistical differences in the response rate (83% versus 73%), progression-free survival time (median, 12.7 months versus 8.1 months,) or overall survival time (median, 24.7 months versus 16.4 months).

Conclusion. Patients with complex EGFR mutations with the classical mutation pattern had the same response rate, progression-free survival duration, and overall survival time as those with single classical mutations. EGFR TKIs may be the choice of treatment for this type of lung adenocarcinoma.