Gefitinib for the treatment of non-small-cell lung cancer.
BACKGROUND
The epidermal growth factor receptor (EGFR) is a leading target for treatment of non-small-cell lung cancer (NSCLC). Recent trials of the small-molecule EGFR inhibitor gefitinib have now more clearly defined indications for usage, and clinical and molecular factors predictive of benefit.


METHODS
A systematic search of the literature (Medline, ASCO, WCLC meeting abstracts) was performed from January 2000 to January 2010. The Phase III INTEREST study found gefitinib in unselected, pretreated patients was not inferior to docetaxel chemotherapy in overall survival, offering improved quality of life and superior toxicity profile. The Phase III IPASS study demonstrated improved progression-free survival with gefitinib compared with paclitaxel-carboplatin chemotherapy in chemotherapy-naive, never/light ex-smokers with adenocarcinoma histology. Stratifying for EGFR mutation revealed mutation-positive patients had superior outcomes with gefitinib compared with chemotherapy. Subsequent studies (WJOG4305, NEJ002), selecting only EGFR mutation-positive patients prospectively confirm this finding.


RESULTS
The profile of gefitinib and landmark trials in NSCLC are summarized. How biomarkers may further optimize therapeutic benefit is highlighted.


CONCLUSIONS
Gefitinib is expected to have an important impact on management of pretreated and selected chemotherapy-naive patients with advanced NSCLC. In addition, activating EGFR mutations are proven to be of value for prediction of those who will derive most benefit.
Campbell
Lynn
L
Christie Hospital NHS Foundation Trust, Medical Oncology, Wilmslow Road, Manchester, UK. lrcampbell@doctors.org.uk
Blackhall
Fiona
F
Thatcher
Nicholas
N
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib