Novel Therapies for Metastatic Non-Small Cell Lung Cancer with MET Exon 14 Alterations: A Spotlight on Capmatinib

Abstract

MET exon 14 (METex14) alterations are now an established therapeutically tractable target in non-small cell lung cancer (NSCLC). Recently reported trials of several MET tyrosine kinase inhibitors (TKI) in this patient population have demonstrated promising efficacy data in both the treatment naïve and pre-treated settings and have led to regulatory approvals. This review will focus on practical diagnostic considerations for METex14 alterations, the trial evidence for capmatinib in this molecular subset including dosing and toxicity management, and the future therapeutic landscape of METex14 altered NSCLC.

Optimal Treatments for NSCLC Patients Harboring Primary or Acquired MET Amplification

“…Clinical trials with patients harboring MET alterations might provide these patients with more options. 30 In the GEOMETRY trial, capmatinib (INC280) achieved an inspiring 12.6-month duration of response (DOR) as first-line treatment and a 9.7-month DOR as second-line treatment. Other trials for tepotinib (VISION trial) and savolitinib (NCT02897479) proved the convincing efficacy of these TKIs.…”

Spotlight on Tepotinib and Capmatinib for Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation

“…Capmatinib also targets and selectively binds the MET tyrosine kinase, including mutations produced by exon 14 skipping, and inhibits cancer cell growth driven by MET aberrations ( Figure 1 ). 34 Capmatinib inhibits phosphorylation of MET and its downstream effects, thus inhibiting tumor proliferation and inducing apoptosis in MET-dependent tumor cell lines. 35 On May 6 2020, capmatinib was approved by the FDA for use in adults with metastatic NSCLC with a METex14 skipping mutation.…”