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.
MET second-site mutations in EGFR-mutant, MET-amplified non-small cell lung cancer after resistance to combinatorial targeted therapy.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20730)
Author(s): Jia-Tao Cheng, Jinji Yang, Yilong Wu; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, P. R. China, Guangdong, China; Guangdong Provincial People's Hospital, Guangzhou, China
Background: MET second-site mutations were previously reported in a few cases of MET-amplified or exon 14-mutant advanced non-small-cell lung cancer (NSCLC) treated with MET inhibitors. However, both the frequency of MET second-site mutations and clinical outcome of patients with such genetic alterations have not been investigated, particularly in EGFR-mutant, MET-amplified advanced NSCLC treated with combinatorial targeted therapy. Methods: Retrospectively, from November 2016 to January 2019, 22 patients with EGFR-mutant, MET-amplified advanced NSCLC had sufficient tumor samples after resistance to a combinatorial therapy with both EGFR and MET inhibitors. All tissue samples were detected using Next-generation sequencing (NGS). The progression-free survival (PFS) was calculated the start of subsequent treatment to progressive disease or death from any cause. The overall survival (OS) was calculated from the start of subsequent treatment to death from any cause. Last follow-up was on January 31, 2019. Results: Five kinds of MET second-site mutations were found in 7 patients: D1246N D1228N, D1228H, D1231Y and Y1230H. The frequency of MET second-site mutations was 31.8% (7/22). The median PFS and OS were 3.7 (95%CI: 1.13-6.3) months and 6.9 (95%CI: 0.2-13.7) months respectively. The ORR of EGFR TKIs plus cabozantinib for suchsecond-site mutaant patients was 50% (2/4). However, the ORR of other treatments was 0% (0/3), Two of them received single agent cabozantinib, and PFS was 0.7 and 1.7 months respectively. One had a PFS of 2.5 months with pemetrexed/carboplatin plus bevacizumab. Conclusions:MET second-site mutation might be one of the commonly-seen molecular mechanisms of acquired resistance to combinatorial targeted therapy in EGFR-mutant, MET-amplified advanced NSCLC. Patients with such mutations could respond to cabozantinib plus EGFR TKI. Further more investigations are warranted to improve the efficacy.