Cancer Res Treat.  2021 Oct;53(4):1024-1032. 10.4143/crt.2020.1331.

The Clinical Impact of Capmatinib in the Treatment of Advanced Non–Small Cell Lung Cancer with MET Exon 14 Skipping Mutation or Gene Amplification

• Choi W
• Park SY
• Lee Y
• Lim KY
• Park M
• Lee GK
• Han JY

• KMID: 2521578
• DOI: http://doi.org/10.4143/crt.2020.1331

Abstract

Purpose
Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.
Materials and Methods
Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed.
Results
A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123).
Conclusion
Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

Keyword

Non-small-cell lung carcinoma; c-MET; Capmatinib

Figure

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  Fig. 1 Correlation of MET immunohistochemistry and gene copy numbers. Scatter plot of MET gene copy number values classified by immunohistochemistry staining results. A dotted line indicates the gene copy number threshold value of 10 copies per cell. Statistical analyses were performed using an ANOVA test. METex14, MET exon 14 skipping mutation.

• 

  Fig. 2 Kaplan-Meier plots for overall survival. Kaplan-Meier plots for overall survival in all study patients (n=72) stratified by study groups (log-rank test, p=0.457) (A), patients with MET gene copy number (GCN) ≥ 10 or MET exon 14 skipping mutation (METex14) (n=14) stratified by capmatinib treatment (log-rank test, p=0.025) (B), and patients untreated with capmatinib (n=59) stratified by MET GCN levels (GCN > 10) and the presence of MET- ex14 (log-rank test, p=0.123) (C). mOS, median overall survival.

Reference

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