Epidermal growth factor receptor inhibition in lung cancer: status 2012.
Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing.
Department of Medicine, Division of Medical Oncology and Department of Pathology, University of Colorado Cancer Center, 12801 E. 17th Avenue, Aurora, CO 80045, USA. fred.hirsch@ucdenver.edu
Fred R
FR
Hirsch
Pasi A
PA
Jänne
Wilfried E
WE
Eberhardt
Federico
F
Cappuzzo
Nick
N
Thatcher
Robert
R
Pirker
Hak
H
Choy
Edward S
ES
Kim
Luis
L
Paz-Ares
David R
DR
Gandara
Yi-Long
YL
Wu
Myung-Ju
MJ
Ahn
Tetsuya
T
Mitsudomi
Frances A
FA
Shepherd
Tony S
TS
Mok
D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors
D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors