Journal
NEW ENGLAND JOURNAL OF MEDICINE
Volume 383, Issue 10, Pages 944-957Publisher
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa2002787
Keywords
-
Categories
Funding
- Novartis Pharmaceuticals
- Korea Health Promotion Institute [2010700-1] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
BACKGROUND Among patients with non-small-cell lung cancer (NSCLC),METexon 14 skipping mutations occur in 3 to 4% andMETamplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients withMET-dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy andMETstatus (METexon 14 skipping mutation orMETamplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with aMETexon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients withMETamplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients withMETamplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with aMETexon 14 skipping mutation, particularly in those not treated previously. The efficacy inMET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available