Correlation of molecular markers including mutations with clinical outcomes in advanced non small cell lung cancer (NSCLC) patients (pts) treated with gefitinib, chemotherapy or chemotherapy and gefitinib in IDEAL and INTACT clinical trials
Lynch, T.J.; Bell, D.; Haber, D.; Johnson, D.; Giaccone, G.; Fukuoka, M.; Kris, M.; Herbst, R.; Krebs, A.; Ochs, J.
Journal of Clinical Oncology 23(16_Suppl): 7006-7006
2016
ISSN/ISBN: 0732-183X
PMID: 27943795
Accession: 057521470
NlmCategory="UNASSIGNED">7006 Background: Gefitinib, a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase leads to major responses in ≤19% of pts; symptoms improve in nearly half (IDEAL I & 2). When combined with systemic chemotherapy, no therapeutic gain was seen compared to chemotherapy alone (INTACT I & II). Somatic activating mutations in the EGFR-TK domain (exons 18-21) have been found in pts with a dramatic, rapid response to gefitinib (Lynch et al, Paez et al, Pao, et al). Tumor samples were obtained from patients enrolled on the IDEAL studies (monotherapy for previously treated patients) and INTACT studies (randomized trials of chemotherapy +/- gefitinib in untreated advanced stage patients). Using standard sequencing protocols we sequenced exons 18-21 of EGFR TK domain. Selected samples were analyzed for ras and p53 mutations. Correlations were made between mutational status, therapies and outcome measures including tumor response and survival. Among 416 IDEAL patients, 119 had available tumor sample, 78 were fully evaluable and validated for exons 18-21. Fourteen mutations were detected (11 deletion, 3 point mutations). Of the 14 pts with mutations: adenocarcinoma (12), women (8), smokers or former smokers (9), and objective responses (6). Among 2130 INTACT patients, there were 672 available tumor samples. Of 312 evaluable samples to date, 32 mutations have been detected (22 deletion, 10 point mutations). Of the 32 pts with mutations: adenocarcinoma (25), men (17), never smokers (9); 15/23 had objective responses to treatment (9 inevaluable). EGFR, ras and p53 mutation status will be correlated wtih treatment received (chemotherapy, chemotherapy + gefitinib, or gefitinib alone). Clinical outcomes including progression free and overall survival by mutation status will also be presented. Prospective studies examining the role of mutational status and other biomarkers with clinical outcome including response and survival are underway. [Table: see text].