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Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non–Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib

Authors' Affiliations: ¹ Lowe Center of Thoracic Oncology, Department of Medical Oncology and ² Department of Medical Oncology, Dana-Farber Cancer Institute; Departments of ³ Medicine and ⁴ Pathology, Harvard Medical School; Departments of ⁵ Medicine and ⁶ Pathology, Massachusetts General Hospital; ⁷ Massachusetts General Hospital Cancer Center; Departments of ⁸ Pathology and ⁹ Medicine, Brigham and Women's Hospital; ¹⁰ Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; ¹¹ Laboratory for Molecular Medicine, Harvard-Partners Center for Genetics and Genomics, Cambridge, Massachusetts; and ¹² Ireland Cancer Center, University Hospitals of Cleveland, Case School of Medicine, Cleveland, Ohio

Requests for reprints: Pasi A. Jänne, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, D1234, 44 Binney Street, Boston, MA 02115. Phone: 617-632-6076; Fax: 617-632-5786; E-mail: pjanne{at}partners.org.

Purpose: Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non–small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib.

Experimental Design: Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations. Patients with exon 19 deletion or L858R mutations were identified. The response rate, time to progression, and overall survival were determined for the two groups.

Results: We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib. Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation (38 versus 17 months; P = 0.04). There were also trends toward higher response rate (73% versus 50%) and improved time to progression (24 versus 10 months) for the patients with an exon 19 deletion, although these were not independently significant in a multivariate analysis. A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [18 of 23 (78%) versus 3 of 9 (33%); P = 0.04]. No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients.

Conclusions: Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors.

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