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Lung Cancer. 2011 Mar;71(3):249-57. doi: 10.1016/j.lungcan.2010.12.008. Epub 2011 Jan 8.

Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating epidermal growth factor receptor mutation: Review of the evidence.

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  • 1Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy. cgridelli@libero.it

Abstract

Gefitinib is a small molecule tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR). Since 2004, it was clear that a substantial proportion of non-small-cell lung cancers (NSCLC) obtaining objective response when treated with gefitinib harbour activating mutations in the EGFR gene. Consequently, EGFR mutation has been widely studied, together with other molecular characteristics, as a potential predictive factor for gefitinib efficacy. As of August 2010, four East Asian randomized phase III trials comparing gefitinib to platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) eligible for first-line treatment have been reported or published. Two of these trials were conducted without a molecular selection in patients with clinical characteristics (adenocarcinoma histology, never or light smoking) characterized by higher prevalence of EGFR mutation. In patients selected for the presence of tumor harbouring EGFR mutation, the administration of first-line gefitinib, as compared to standard chemotherapy, was associated with longer progression-free survival, higher objective response rate, a more favourable toxicity profile and better quality of life. The relevant improvement in progression-free survival with first-line administration of gefitinib has been confirmed in the other two randomized trials, dedicated to cases with EGFR mutation. In July 2009, European Medicines Agency granted marketing authorization for gefitinib for the treatment of locally advanced or metastatic NSCLC with sensitizing mutations of the EGFR gene, across all lines of therapy. Gefitinib currently represents the best first-line treatment option for this molecularly selected subgroup of patients.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PMID:
21216486
[PubMed - indexed for MEDLINE]
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