Characterization of MET exon 14 alteration and association with clinical outcomes of crizotinib in Chinese lung cancers. (October 2020)

• Record Type: Journal Article
• Authors: Yang, Haiyan; Zhou, Zhen; Lin, Li; Yang, Mingxia; Li, Chong; Li, Ziming; Yu, Xinmin; Lizaso, Analyn; Han-Zhang, Han; Li, Bing; Xiang, Jianxing; Mao, Xinru; Xu, Qinqin; Zhang, Yongchang; Yang, Nong
• Is Part Of: Lung cancer. Volume 148(2020)
• Page Start: 113
• Page End: 121
• Publication Date: 2020-10
• Subjects: MET exon 14 alteration -- Crizotinib -- TP53 -- MET amplification -- Non-small-cell lung cancer -- MET Y1003C; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.08.009
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: MET exon 14 alterations have a prevalence of 1.1 % among Chinese patients. MET-exon-14-altered NSCLC had a longer PFS with front-line crizotinib than with chemotherapy. Different MET exon 14 variants and concurrent TP53 alteration did not affect survival outcomes. Concurrent MET amplification was associated with poorer PFS for crizotinib. MET Y1003C mutation was identified and demonstrated a clinical response to crizotinib. Abstract: Background: Most studies on MET exon 14 ( MET -ex14) alteration, defined as an oncogenic driver, have been carried out among Caucasians; similar studies among Chinese people are limited. Methods: We retrospectively analyzed the genomic profiles of 11, 306 Chinese patients with various stages of lung cancer to investigate the prevalence of MET -ex14. Survival outcomes were analyzed in evaluable patients who received front-line crizotinib (n = 44) or chemotherapy (n = 14). Results: MET -ex14 alterations were identified in 125 patients, a frequency of 1.1 %, which is much lower than that in Caucasians (∼2.7 %). We found that MET -ex14 alterations were more likely to be detected in older patients (median age 69.0 years, p <0.001). Among evaluable patients harboring MET -ex14 alterations, longer progression-free survival (PFS) was observed with crizotinib than with chemotherapy (8.5 months versus 4.0 months, p = 0.041), but there was no difference in overall survival (OS, 11.3 months versus 12.0 months, p = 0.66). No significant difference in PFS or OS was found among MET splice-site variants or when there were concurrent TP53 alterations. Concurrent MET amplification results in a shorter PFS (4.2 months versus 8.5 months, p = 0.029) but a comparable OS (7.8 months versus 14.0 months, p = 0.12). Patients with undetectable baseline plasma MET -ex14 had a trend of longer PFS ( p = 0.097) but comparable OS ( p = 0.18). A novel MET Y1003C mutation was detected and demonstrated a clinical response to crizotinib. Conclusions: Our study demonstrated a prevalence of 1.1 % for MET- ex14 alterations among the Chinese population. Our study also contributes to a better understanding of molecular factors that are associated with clinical outcomes of patients with MET exon 14 alterations.