Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor Are Associated with Improved Survival in Gefitinib-Treated Chemorefractory Lung Adenocarcinomas

• Miguel Taron

  1Catalan Institute of Oncology,

• Yukito Ichinose

  3National Kyushu Cancer Center,

• Rafael Rosell

  1Catalan Institute of Oncology,

• Tony Mok

  5Prince of Wales Hospital,

• Bartomeu Massuti

  7Hospital General de Alicante, Alicante, Spain;

• Lurdes Zamora

  1Catalan Institute of Oncology,

• Jose Luis Mate

  2Pathology Department, Hospital Germans Trias i Pujol, Badalona, Spain;

• Christian Manegold

  8Heidelberg University Medical Center, Mannheim, Mannheim, Germany;

• Mayumi Ono

  4Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;

• Cristina Queralt

  1Catalan Institute of Oncology,

• Thierry Jahan

  9Comprehensive Cancer Center, University of California, San Francisco, California; and

• Jose Javier Sanchez

  10Autonomous University of Madrid, Madrid, Spain

• Maria Sanchez-Ronco

  10Autonomous University of Madrid, Madrid, Spain

• Victor Hsue

  6St. Teresa Hospital Cancer Centre, Hong Kong, China;

• David Jablons

  9Comprehensive Cancer Center, University of California, San Francisco, California; and

• Jose Miguel Sanchez

  1Catalan Institute of Oncology,

• Teresa Moran

  1Catalan Institute of Oncology,

抄録

Purpose: Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) confer a strong sensitivity to gefitinib, a selective tyrosine kinase inhibitor of EGFR. Experimental Design: We examined EGFR mutations at exons 18, 19, and 21 in tumor tissue from 68 gefitinib-treated, chemorefractory, advanced non–small cell lung cancer patients from the United States, Europe, and Asia and in a highly gefitinib-sensitive non–small cell lung cancer cell line and correlated their presence with response and survival. In addition, in a subgroup of 28 patients for whom the remaining tumor tissue was available, we examined the relationship among EGFR mutations, CA repeats in intron 1 of EGFR, EGFR and caveolin-1 mRNA levels, and increased EGFR gene copy numbers. Results: Seventeen patients had EGFR mutations, all of which were in lung adenocarcinomas. Radiographic response was observed in 16 of 17 (94.1%) patients harboring EGFR mutations, in contrast with 6 of 51 (12.6%) with wild-type EGFR (P < 0.0001). Probability of response increased significantly in never smokers, patients receiving a greater number of prior chemotherapy regimens, Asians, and younger patients. Median survival was not reached for patients with EGFR mutations and was 9.9 months for those with wild-type EGFR (P = 0.001). EGFR mutations tended to be associated with increased numbers of CA repeats and increased EGFR gene copy numbers but not with EGFR and caveolin-1 mRNA overexpression (P = not significant). Conclusions: The presence of EGFR mutations is a major determinant of gefitinib response, and targeting EGFR should be considered in preference to chemotherapy as first-line treatment in lung adenocarcinomas that have demonstrable EGFR mutations.

収録刊行物

• Clinical Cancer Research

  Clinical Cancer Research 11 (16), 5878-5885, 2005-08-15

  American Association for Cancer Research (AACR)

キーワード

• Cancer Research
• Oncology

詳細情報

• CRID: 1362544421255112064
• NII論文ID: 30018691395
• DOI: 10.1158/1078-0432.ccr-04-2618
• ISSN: 15573265
• ISSN: 10780432
• Web Site: https://aacrjournals.org/clincancerres/article-pdf/11/16/5878/1957630/5878-5885.pdf
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