Originally published as JCO Early Release 10.1200/JCO.2008.16.7254 on September 15 2008

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EGFR Mutations Predict Survival Benefit From Gefitinib in Patients With Advanced Lung Adenocarcinoma: A Historical Comparison of Patients Treated Before and After Gefitinib Approval in Japan

Toshimi Takano, Tomoya Fukui, Yuichiro Ohe, Koji Tsuta, Seiichiro Yamamoto, Hiroshi Nokihara, Noboru Yamamoto, Ikuo Sekine, Hideo Kunitoh, Koh Furuta, Tomohide Tamura

From the Division of Internal Medicine; Clinical Laboratory Division; Statistics and Cancer Control Division, Research Center for Cancer Prevention and Screening; and Clinical Support Laboratory, National Cancer Center Hospital; and the Department of Medical Oncology, Teikyo University School of Medicine, Tokyo, Japan

Corresponding author: Yuichiro Ohe, MD, Division of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; e-mail: yohe{at}ncc.go.jp

Purpose This study evaluated whether the presence of epidermal growth factor receptor (EGFR) mutations is a predictive marker for survival benefit from gefitinib and/or a prognostic marker in patients with advanced lung adenocarcinoma.

Patients and Methods Overall survival (OS) was compared between patients with advanced lung adenocarcinoma who began first-line systemic therapy before and after gefitinib approval in Japan (January 1999 to July 2001 and July 2002 to December 2004, respectively). Deletional mutations in exon 19 or the L858R mutation in exon 21 of EGFR were evaluated using high-resolution melting analysis.

Results EGFR mutations were detected in 136 (41%) of the 330 patients included in this study. OS was significantly longer among the EGFR-mutant patients treated after gefitinib approval compared with the OS of patients treated before gefitinib approval (median survival time [MST], 27.2 v 13.6 months, respectively; P < .001), whereas no significant survival improvement was observed in patients without EGFR mutations (MST, 13.2 v 10.4 months, respectively; P = .13). A significant interaction between the presence of EGFR mutations and a survival improvement was seen (P = .045). Among patients treated before gefitinib approval, those with EGFR mutations lived longer than those without EGFR mutations (MST, 13.6 v 10.4 months, respectively; P = .034). The response rates to first-line cytotoxic chemotherapy were not significantly different between patients with and without EGFR mutations (31% v 28%, respectively; P = .50).

Conclusion EGFR mutations significantly predict both a survival benefit from gefitinib and a favorable prognosis in patients with advanced lung adenocarcinoma.

published online ahead of print at www.jco.org on September 15, 2008.

Supported by a program for the Promotion of Fundamental Studies in Health Sciences of the Pharmaceuticals and Medical Devices Agency; a Health and Labor Science Research Grant from the Ministry of Health, Labor and Welfare, Japan; and a Grant-in-Aid for Young Scientists from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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