P1.02-058 EGFR Amplification and Sensitizing Mutations Correlates with Survival from Erlotinib in Lung Adenocarcinoma Patients (MutP-CLICAP)

Abstract

Tumor heterogeneity, which causes different EGFR mutation abundance, is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. Frequent EGFR amplification and its common affection in EGFR mutant allele promote the hypothesis that EGFR mutant abundance might be determined by EGFR copy number variation and therefore examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment. 72 lung ADC patients who harbored EGFR activating mutations and received erlotinib as first line treatment, were examined for EGFR amplification by FISH. EGFR mutational and copy number status were compared with response, overall-survival (OS), and progression-free-survival (PFS). Median age was 62-yo (r, 20-87 years), 53 patients were females (73%), and 89% have common mutations. Twenty-two (30.6%) samples with EGFR activating mutations were identified with EGFR amplification. EGFR amplification was more frequent in patients with exon 19 deletion (p=0.05) and in those with better performance status (p=0.01). Patients with EGFR gene amplification had a significantly longer PFS than those without [(25.2 months, 95%CI 22.0-38.5) vs. (12.4 months, 95%CI 5.3-19.5); p=0.002] as well as better OS [(EGFR amplified 37.8 months, 95%CI 30.9-44.7) vs. (EGFR non-amplified 27.1 months, 95%CI 12.8-41.3); p=0.009]. EGFR amplification significantly influenced the response to erlotinib (p=0.0001). EGFR amplification occurs in one third of patients with lung ADC harboring EGFR activating mutations, and could serve as an indicator for better response and survival from EGFR-TKI treatment.