The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer

Autor: C.L. Watkins, A.A. Armour
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: European Respiratory Review, Vol 19, Iss 117, Pp 186-196 (2010)
Druh dokumentu: article
ISSN: 0905-9180
1600-0617
Popis: As the first approved epidermal growth factor receptor (EGFR)-targeted therapy for nonsmall cell lung cancer (NSCLC), the clinical development of gefitinib was complex. Advances in scientific understanding of the target biology during its clinical development enabled the identification of a biomarker to define patients most likely to derive benefit from gefitinib. Initial phase II trials showed clinically meaningful anti-tumour activity in 12–18% of unselected pretreated patients with advanced NSCLC at the optimum biological dose (250 mg). Subgroup analyses of these and subsequent phase III trials in unselected patients suggested that EGFR mutation and some clinical characteristics associated with a higher incidence of EGFR mutation (Asian ethnicity, adenocarcinoma histology, never-smoking and female sex) were linked with increased response to gefitinib. Consequently, the IRESSA Pan-Asia Study (IPASS) was conducted in never-smokers or former light-smokers in East Asia who had adenocarcinoma of the lung. IPASS showed that EGFR mutation was the strongest predictor of improved progression-free survival (mutation-positive subgroup hazard ratio (HR) 0.48, 95% CI 0.36–0.64 (p
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