Ongoing first-line studies of epidermal growth factor receptor tyrosine kinase inhibitors in select patient populations.
The epidermal growth factor receptor (EGFR) has emerged as an attractive therapeutic target for patients with non-small cell lung cancer (NSCLC). However, despite its almost universal presence in NSCLC tumors, therapeutic inhibition of EGFR has resulted in significant tumor regressions in only 10% to 20% of patients. Several investigations over the last 12 months have uncovered somatic mutations in EGFR that underlie the sensitivity to EGFR inhibitors. Somatic mutations in EGFR are found more frequently in patients with adenocarcinomas, nonsmokers, patients of Asian ethnicity, and in females. These same subgroups of patients have previously been identified as those most likely to respond to EGFR tyrosine kinase inhibitors (TKIs). Information to date suggests that patients with EGFR mutations will derive the greatest benefit as measured by response rate, time to progression, and survival from EGFR inhibitors. In addition, data on EGFR amplification as a predictor of outcome with EGFR TKI therapy is also emerging. These therapeutic approaches are now being introduced as initial therapy for specific subgroups of patients defined by either clinical or molecular characteristics that predict for response to EGFR TKIs. The rationale and design of these trials will be reviewed.
Jänne
Pasi A
PA
Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, MA 02115, USA. pjanne@partners.org
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018579:Patient Selection; D011379:Prognosis; D013534:Survival
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors