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Crizotinib in Patients With MET-Amplified NSCLC.

D Ross Camidge1, Gregory A Otterson2, Jeffrey W Clark3

  • 1University of Colorado Cancer Center, Aurora, Colorado.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|March 6, 2021
PubMed
Summary

High-level MET amplification in non-small cell lung cancer (NSCLC) patients correlated with better response to crizotinib. Combined diagnostics may identify patients most likely to benefit from MET-targeted therapy.

Keywords:
CrizotinibMET amplificationNext-generation sequencingNon–small cell lung cancerOncogenic driver mutation

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Area of Science:

  • Oncology
  • Genetics

Background:

  • MET amplification is a rare but actionable driver in non-small cell lung cancer (NSCLC).
  • Understanding MET amplification's impact on treatment response is crucial for personalized medicine.

Purpose of the Study:

  • To investigate the clinical activity of crizotinib in NSCLC patients with varying levels of MET amplification.
  • To assess the correlation between MET amplification levels and treatment outcomes.

Main Methods:

  • 38 NSCLC patients with MET-to-CEP7 ratio ≥1.8 received crizotinib.
  • Patients were categorized into high, medium, and low MET amplification groups.
  • Objective response rate (ORR), duration of response, and progression-free survival were evaluated.

Main Results:

  • High-level MET amplification (n=21) showed the highest ORR (38.1%) and longest median progression-free survival (6.7 months).
  • Patients with concurrent MET exon 14 alterations showed objective responses.
  • No responses were observed in patients with concurrent KRAS, BRAF, or EGFR mutations.

Conclusions:

  • High-level MET-amplified NSCLC patients demonstrated the best response to crizotinib.
  • Combined diagnostic approaches for MET and other oncogenes could improve patient selection for crizotinib therapy.