Prognosis and Concurrent Genomic Alterations in Patients With Advanced NSCLC Harboring MET Amplification or MET Exon 14 Skipping Mutation Treated With MET Inhibitor: A Retrospective Study

• Published in: Frontiers in oncology Vol. 11; p. 649766
• Main Authors: Liu, Li, Kalyani, Farhin Shaheed, Yang, Haiyan, Zhou, Chunhua, Xiong, Yi, Zhu, Songlin, Yang, Nong, Qu, Jingjing
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 24-06-2021
• Subjects: concurrent genomic alterations; MET amplification; MET exon 14 skipping mutation; MET inhibitor; non-small cell lung cancer; Oncology; non-small cell lung cancer; MET amplification; MET exon 14 skipping mutation; concurrent genomic alterations; MET inhibitor
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.649766

MET amplification or METex14 skipping mutations are uncommon oncogenic events in NSCLC patients. Clinicopathological characteristics, concurrent gene alterations, and prognosis of MET TKIs in these patients are yet to be elucidated.
We retrospectively analyzed the genomic profiles of 43 MET amplifications or 31 METex14 skipping mutations in NSCLC patients with no previous treatment with EGFR TKIs. Survival outcomes were analyzed in evaluable patients receiving MET TKI treatment: MET amplification cohort (n = 29) and METex14 skipping mutation cohort (n = 29).
Among evaluable patients, a shorter PFS was observed in the MET amplification cohort than in the METex14 skipping mutation cohort (7.0 months
11.0 months, P = 0.043). Concurrent mutations in both cohorts resulted in a statistically significant shorter PFS (MET amplification: 3.5 months
8.0 months, P = 0.038, METex14 skipping mutation: 7.0
NR months, P = 0.022). However, a statistically significant OS (17.0 months
20.0 months, P = 0.044) was only observed in the MET amplification cohort. TP53, the most common concurrent mutation in both cohorts, was associated with worse survival outcomes as compared to the wild type. The MET amplification cohort with a concurrent PIK3CA mutation exhibited primary resistance to MET TKIs and showed disease progression (80%).
MET TKIs could be a better treatment option for patients with METex14 skipping mutations. Concurrent mutations may deteriorate the PFS of MET TKIs in NSCLC patients with MET amplification or METex14 skipping mutations. PIK3CA mutations may confer primary resistance to MET TKIs in patients with MET amplification.