Mechanisms of primary resistance to icotinib in Chinese non-small-cell lung cancer patients with EGFR uncommon mutations: A multicenter study.

Abstract

e20501 Background: Previous case series, retrospective studies and pooled survey studies have investigated the clinical efficacies of EGFR-TKIs in patients harboring EGFR uncommon mutations. However, part of patients with EGFR uncommon mutations do not exhibit objective responses to EGFR TKIs (primary resistance). The mechanism of primary resistance to icotinib in EGFR uncommon mutations NSCLC has not been clearly understood. Methods: We screened 3279 patients with NSCLC for EGFR uncommon mutations. Among them, 106 patients received icotinib treatment, and a total of 69 patients with stage IIIb-IV EGFR uncommon mutations NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring to icotinib, in including formalin-fixed paraffin-embedded (FFPE) samples, serum samples and serous effusions. We used targeted NGS to detect genes status of patients. Results: Among 69 patients treated with icotinib, 69.57% (48/69) developed acquired resistance, and 30.43% (21/69) had primary resistance. Using the specimens at the baseline, there were 6(28.57%) patients with EGFR extracellular domain mutation, 5(23.81%) patients with BCL2L11 loss (BIM deletion polymorphism), 3(14.29%) patients with MET amplification, 1(4.76%) patient with ERBB2 amplification, 1(4.76%) patient with MYC amplification, 1(4.76%) patient with PTEN mutation, 1(4.76%) patient with PIK3CA mutation, and 3 (14.29%) patients with unknown status. Conclusions: EGFR extracellular domain mutation, BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, PIK3CA mutations), MET amplification, ERBB2 amplification or MYC amplification might contribute to molecular mechanisms of primary resistance to icotinib in EGFR uncommon mutations NSCLC. The complexity and heterogeneity of EGFR uncommon mutations NSCLC that may confer primary resistance to icotinib using NGS platform.