P3-144: Docetaxel, Gemcitabine, and Cetuximab in Untreated Advanced Non-Small Cell Lung Cancer

David R. Spigel, F Anthony Greco, Howard A. Burris, Denise A. Yardley, Elizabeth R. Vazquez, John D. Hainsworth
2007 Journal of Thoracic Oncology  
Mutations in the tyrosine kinase domain of EGFR have been found to be associated with sensitivity of NSCLC to gefitinib. We analyzed the status of EGFR and KRAS mutations in advanced NSCLC to examine their relationship with the response to gefitinib. Methods: Between December 2001 and December 2004, a total of 199 NSCLC patients treated with gefitinib (250 mg/day) at our institution. Sixty patients were assessable for response and had paraffin-embedded tumor tissue adequate for mutational
more » ... is. Exons 18, 19, and 21 of the EGFR gene and exon 2 of the KRAS gene were sequenced. The results were then correlated with clinical features and outcome, including tumor response and patient survival. Results: EGFR mutations were found in 14 patients (23%). Among them, 11 were in three hot-spots (G719, L747-A750, and L858), and novel T847A and V851L were observed in three patients. Response rate in patients with EGFR mutation was 79% (11 of 14 patients), in contrast to 22% (10 of 46 patients) in patients without mutation (P < .001). Moreover, these 14 patients with EGFR mutation had significantly prolonged time to progression (TTP; 7.7 v 2.4 months; P = .032). Patients with EGFR mutation also had better overall survival (OS), although it did not reach statistical significance (19.2 v 13.6 months; P = .25). KRAS mutations were present in 7 of 60 patients (12%) but not in any tumors with EGFR mutation. Interestingly, response rates were similar for patients with or without KRAS mutation (43% v 34%; P = .23). In the multivariate analysis, EGFR mutation and adenocarcinoma histology were factors significantly associated with better response and TTP. Conclusions: EGFR mutation is significantly associated with a response to gefitinib and a longer TTP in NSCLC patients. Although response rates were not different according to the presence of the KRAS mutation, whether KRAS mutational status can be used to predict response to gefitinib is still not clear.
doi:10.1097/01.jto.0000284119.51207.2e fatcat:u57ughwrevc6rf6msx57gokuva