A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance

• DOI: 10.3389/fonc.2021.722039
• Publication Date: 2021-10-01T05:47:43Z
• Authors: Li Liu; Jingjing Qu; Jianfu Heng; Chunhua Zhou; Yi Xiong; Haiyan Yang; Wenjuan Jiang; Liang Zeng; Songlin Zhu; Yongchang Zhang; Jiarong Tan; Chengping Hu; Pengbo Deng; Nong Yang
• Keywords: T790M; Progression-free survival; Regimen

MET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI remains controversial. Our study compared three strategies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who were detected MET-amp at progression using next-generation sequencing.Of 70 included in study, 38 received + crizotinib, 10 crizotinib monotherapy, and 22 chemotherapy. Clinical outcomes molecular profiles analyzed.The objective response rate was 48.6% group, 40.0% monotherapy 18.2% chemotherapy group. Patients had significantly longer progression-free survival than those or (5.0 vs. 2.3 2.9 months, p = 0.010), but overall comparable (10.0 4.1 8.5 0.088). TP53 mutation (58.5%) EGFR-amp (42.9%) frequent concurrent mutations of cohort. Progression-free either (n 17) (6.0 0.009) 13) 1.2 2.4 0.016) group other two regimen. Potential mechanisms EGFR-T790M 2), EGFR-L718Q 1), EGFR-S645C MET-D1228H BRAF-V600E NRAS-Q61H KRAS-amp ERBB2-amp CDK4-amp MYC-amp 1).Our provides real-world clinical evidence from a large cohort that simultaneous inhibition EGFR could be more effective therapeutic therapy.