|
|||||
|
|
||||||
Originally published as JCO Early Release 10.1200/JCO.2007.14.8494 on May 5 2008 © 2008 American Society of Clinical Oncology. First-Line Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer Harboring Somatic EGFR Mutations
From the Massachusetts General Hospital Cancer Center; Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital; Department of Pathology, Massachusetts General Hospital; Department of Biostatistics, Massachusetts General Hospital, Boston; Harvard Medical School/Partners Health Care Center for Genetics and Genomics, Cambridge, MA; University of Washington, Seattle, WA; Sarah Cannon Research Institute, Nashville, TN; Fletcher Allen Health Care, Burlington, VT; Fairfax-Northern Virginia Hematology-Oncology PC, Fairfax, VA; Texas Oncology/Sammons Cancer Center, Dallas, TX; University of Pennsylvania, Philadelphia, PA; and the Mt Kisco Medical Group, Mt Kisco, NY Corresponding author: Lecia V. Sequist, MD, MPH, Massachusetts General Hospital Cancer Center, 32 Fruit St, Yawkey Suite 7B, Boston, MA 02114; e-mail: lvsequist{at}partners.org Purpose: Somatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non–small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms.
Patients and Methods: Chemotherapy-naïve patients with advanced NSCLC with Results: Ninety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification. Conclusion: First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care. published online ahead of print at www.jco.org on May 5, 2008. Supported by a research grant from AstraZeneca, study IRUSIRES0483. Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007. Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org. Authors disclosures of potential conflicts of interest and author contributions are found at the end of this article. Related Editorial
This article has been cited by other articles:
|
||||||||||||||||||||||||
|
|||||||||||
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|