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Clinical Cancer Research Vol. 12, 839-844, February 2006
© 2006 American Association for Cancer Research

Cancer Therapy: Clinical

Clinical Course of Patients with Non–Small Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 19 and Exon 21 Mutations Treated with Gefitinib or Erlotinib

Gregory J. Riely1, William Pao1,4, DuyKhanh Pham2, Allan R. Li3, Naiyer Rizvi1, Ennapadam S. Venkatraman5, Maureen F. Zakowski3, Mark G. Kris1, Marc Ladanyi3 and Vincent A. Miller1

Authors' Affiliations: Thoracic Oncology Service, Departments of 1 Medicine, 2 Surgery, and 3 Pathology; 4 Human Oncology and Pathogenesis Program; and 5 Biostatistics Service, Memorial Sloan-Kettering Cancer Center, New York, New York

Requests for reprints: Vincent A. Miller, Thoracic Oncology Service, Department of Medicine, Box 437, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: 212-639-7243; Fax: 1-212-794-4357; E-mail: millerv{at}mskcc.org.

Purpose: In patients with non–small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib. We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib.

Experimental Design: In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival).

Results: The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a "never smoker" (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01).

Conclusions: EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations.




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