Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
EGFR extracellular domain mutation in patients with lung cancer.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20532)
Author(s): Renhua Guo, Dejian Gu, Jun Zhao, Lingjun Zhu, Mingjiu Chen, Shuoyan Liu, Bo Tang, Rongrong Chen, Xuefeng Xia; The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Geneplus-Beijing Institute, Beijing, China; Beijing University School of Oncology Beijing Institute for Cancer Research, Beijing, China; Jiangsu Province Hospital, Nanjing, China; The Second Xiangya Hospital of Central South University, Changsha, China; Fujian Provincial Cancer Hospital, Fuzhou, China; ZiGong No.4 People' s Hosiptal, Zigong, China; Houston Methodist Research Institute, Weill Cornell School of Medicine, Houston, TX
Background: Missense mutations in the EGFR extracellular (EC) domain are found in 10% to 15% of glioblastomas(GBM). However, little is known about EGFR EC domain mutations in lung cancer. In this study, we retrospectively analyzed distribution of EGFR EC domain mutation in lung cancer. Methods: A total of 10100 lung cancer patients were analyzed in this study. EGFR mutations were detected by hybridization capture-based NGS panel sequencing with tumor biopsy, ctDNA or pleural effusion samples. Results: We identified gain-of-function mutations in the EC domain of EGFR in 36 (0.36%, 36/10100) patients with 23 patients carrying EGFR A289D/V/T/Y mutation, 10 patients harboring EGFR R108K/S mutation, 2 patients having EGFR T263P mutation, and 1 patient with EGFR G598R mutation. The EGFR EC domain mutation was detected in 23 patients with lung adenocarcinoma and 13 patients with other types of lung cancer (P = 0.018). Notably, 29 (80.56%) patients were detected with EGFR EC domain mutation and EGFR intracellular kinase domain (KD) mutation (P = 2.15×10-7). The incidence of L858R concomitant EC domain mutation was significantly higher compared with 19del (72.41% vs 17.24%, p = 28.64×10-5) or other EGFR KD mutations (72.41% vs 10.34%, p = 6.79×10-6). To further study whether L858R concomitant with EC domain mutation affected the efficiency of targeted therapy, we analyzed 6 patients who were treated with EGFR-TKIs. Among them, disease control rate of 2 months was 83.33% (5/6). Two patients had 10 months PFS. Three patients have been treated for 2, 5 and 12 months respectively, and are still on treatment. Conclusions: Our study reveals the distribution of EGFR EC domain mutation in lung cancer. EGFR EC domain mutation are more likely to occur concomitantly EGFR KD mutation, especial L858R. Meanwhile, our study shows that concomitant EC domain mutation and L858R may not affect the efficiency of targeted therapy.