Predictive biomarkers in the management of EGFR mutant lung cancer.
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.
Rosell
Rafael
R
Catalan Institue of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain. rrosell@ico.scs.es
Moran
Teresa
T
Cardenal
Felipe
F
Porta
Rut
R
Viteri
Santiago
S
Molina
Miguel Angel
MA
Benlloch
Susana
S
Taron
Miquel
M
D000230:Adenocarcinoma / Q000235:genetics; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D045744:Cell Line, Tumor; D004247:DNA / Q000097:blood / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005091:Exons; D005260:Female; D000077156:Gefitinib; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D017384:Sequence Deletion; D044465:White People / Q000235:genetics
D019313:BRCA1 Protein; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D004247:DNA; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib