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Capmatinib for MET Exon 14–Mutated or MET-Amplified NSCLC
MET exon 14 skipping mutations and MET gene amplifications occur in 3% to 4% and 1% to 6%, respectively, of patients with non–small-cell lung cancer (NSCLC). Preliminary data demonstrated promising efficacy of the highly selective MET-receptor inhibitor capmatinib in patients with MET-dysregulated NSCLC.
Now, investigators have conducted an industry-funded, multicohort, phase II trial (GEOMETRY mono-1) to evaluate the use of capmatinib (400 mg twice daily) in 364 NSCLC patients with a MET exon 14 skipping mutation or MET amplification.
Results were as follows:
- Among treatment-naive patients with MET exon 14 skipping mutations, the overall response rate (ORR; the primary endpoint) was 68%, and the median duration of response was 12.6 months; among those with MET gene amplification of ≥10 copies, the ORR was 40%.
- Among patients pretreated with 1 or 2 prior therapies, the ORR was 41%, and the median duration of response was 9.7 months; among those with MET gene amplification of ≥10 copies, the ORR was 29%.
- No significant efficacy was seen in patients with <10 MET gene copy numbers.
- Of 13 evaluable patients with baseline brain metastases, 7 (54%) had intracranial responses, and 4 (31%) had complete responses; 3 responders had prior brain radiotherapy.
- The most frequent toxicities were grade 1 or 2 peripheral edema (51% of patients), nausea (45%), vomiting, and increased creatinine.
Comment
Capmatinib is now an additional MET-targeted agent that can be used in advanced MET-altered NSCLC. The central nervous system activity is promising, and the toxicity profile is manageable. In a prior phase II trial involving NSCLC patients with MET exon 14 skipping mutation (NEJM JW Oncol Hematol Jul 2020 and N Engl J Med 2020; 383:931), the oral agent tepotinib demonstrated similar results (ORR, 46%; median duration of response, 11.1 months). In the current study, capmatinib also had activity in a cohort of patients with ≥10 copy numbers of the MET gene. Given the new therapeutic options, it is essential to ensure that NSCLC patients receive next-generation sequencing to identify MET alterations.
Citation(s)
Author:
Wolf J et al.
Title:
Capmatinib in MET exon 14–mutated or MET-amplified non–small-cell lung cancer.
Source:
N Engl J Med
2020
Sep
3; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Anne S. Tsao, MD