Universität zu Köln

Wolf, Juergen, Seto, Takashi, Han, Ji-Youn, Reguart, Noemi, Garon, Edward B., Groen, Harry J. M., Tan, Daniel S. W., Hida, Toyoaki, de Jonge, Maja, Orlov, Sergey V., Smit, Egbert F., Souquet, Pierre-Jean, Vansteenkiste, Johan, Hochmair, Maximilian, Felip, Enriqueta, Nishio, Makoto, Thomas, Michael, Ohashi, Kadoaki, Toyozawa, Ryo, Overbeck, Tobias R., de Marinis, Filippo, Kim, Tae-Min, Laack, Eckart, Robeva, Anna, Le Mouhaer, Sylvie, Waldron-Lynch, Maeve, Sankaran, Banu, Balbin, O. Alejandro, Cui, Xiaoming, Giovannini, Monica, Akimov, Mikhail and Heist, Rebecca S. (2020). Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N. Engl. J. Med., 383 (10). S. 944 - 958. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Seto, Takashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Han, Ji-Youn UNSPECIFIED UNSPECIFIED UNSPECIFIED Reguart, Noemi UNSPECIFIED UNSPECIFIED UNSPECIFIED Garon, Edward B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Groen, Harry J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tan, Daniel S. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hida, Toyoaki UNSPECIFIED UNSPECIFIED UNSPECIFIED de Jonge, Maja UNSPECIFIED UNSPECIFIED UNSPECIFIED Orlov, Sergey V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smit, Egbert F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Souquet, Pierre-Jean UNSPECIFIED UNSPECIFIED UNSPECIFIED Vansteenkiste, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hochmair, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Felip, Enriqueta UNSPECIFIED UNSPECIFIED UNSPECIFIED Nishio, Makoto UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Ohashi, Kadoaki UNSPECIFIED UNSPECIFIED UNSPECIFIED Toyozawa, Ryo UNSPECIFIED UNSPECIFIED UNSPECIFIED Overbeck, Tobias R. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Marinis, Filippo UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Tae-Min UNSPECIFIED UNSPECIFIED UNSPECIFIED Laack, Eckart UNSPECIFIED UNSPECIFIED UNSPECIFIED Robeva, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Le Mouhaer, Sylvie UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldron-Lynch, Maeve UNSPECIFIED UNSPECIFIED UNSPECIFIED Sankaran, Banu UNSPECIFIED UNSPECIFIED UNSPECIFIED Balbin, O. Alejandro UNSPECIFIED UNSPECIFIED UNSPECIFIED Cui, Xiaoming UNSPECIFIED UNSPECIFIED UNSPECIFIED Giovannini, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED Akimov, Mikhail UNSPECIFIED UNSPECIFIED UNSPECIFIED Heist, Rebecca S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-319819
DOI:	10.1056/NEJMoa2002787
Journal or Publication Title:	N. Engl. J. Med.
Volume:	383
Number:	10
Page Range:	S. 944 - 958
Date:	2020
Publisher:	MASSACHUSETTS MEDICAL SOC
Place of Publication:	WALTHAM
ISSN:	1533-4406
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language 14 MUTATIONS; OPEN-LABEL; PHASE-III; AMPLIFICATION; CRIZOTINIB; ADENOCARCINOMA; CHEMOTHERAPY; DOCETAXEL; ERLOTINIB; MULTICENTER Multiple languages Medicine, General & Internal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31981