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Predictive biomarkers in the management of EGFR mutant lung cancer.

Authors
  • Rosell, Rafael
  • Moran, Teresa
  • Cardenal, Felipe
  • Porta, Rut
  • Viteri, Santiago
  • Molina, Miguel Angel
  • Benlloch, Susana
  • Taron, Miquel
Type
Published Article
Journal
Annals of the New York Academy of Sciences
Publisher
Wiley (Blackwell Publishing)
Publication Date
Oct 01, 2010
Volume
1210
Pages
45–52
Identifiers
DOI: 10.1111/j.1749-6632.2010.05775.x
PMID: 20973798
Source
Medline
License
Unknown

Abstract

Activating mutations in the form of deletions in exon 19 (del 19) or the missense mutation L858R in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) predict outcome to use of EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. Pooled data from several phase II studies show that gefitinib and erlotinib induce responses in over 70% of NSCLC patients harboring EGFR mutations, with progression-free survival (PFS) ranging from 9 to 13 months. Two studies in Caucasian and Asian patients have confirmed that these subgroups of patients attain PFS up to 14 months. These landmark outcomes have been accompanied by new challenges, primarily the additional role of chemotherapy and the management of tumors with the secondary T790M mutation that confers resistance to EGFR TKIs. Mechanisms of resistance to reversible EGFR TKIs should be further clarified and could be related to modifications in DNA repair.

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