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

• Published in: Frontiers in oncology 2021-10, Vol.11, p.722039-722039
• Main Authors: Liu, Li, Qu, Jingjing, Heng, Jianfu, Zhou, Chunhua, Xiong, Yi, Yang, Haiyan, Jiang, Wenjuan, Zeng, Liang, Zhu, Songlin, Zhang, Yongchang, Tan, Jiarong, Hu, Chengping, Deng, Pengbo, Yang, Nong
• Format: Article
• Language: English
• Subjects: EGFR mutation; EGFR-TKI and crizotinib combination; EGFR-TKI resistance; MET amplification; NSCLC; Oncology
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.722039

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