Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer : clinical and biomarker results from a phase I trial
Schuler, M. (German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany)
Berardi, R. (Università Politecnica delle Marche-Ospedali Riuniti)
Lim, W.-T (National Cancer Centre Singapore)
de Jonge, M. (Erasmus MC Cancer Center, Rotterdam)
Bauer, Todd M (Sarah Cannon Research Institute, and Tennessee Oncology)
Azaro, Analía (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Gottfried, M. (Oncology Institute of Meir Medical Center)
Han, J.Y (Center for Lung Cancer, National Cancer Center (Corea del Sud))
Lee, D. H. (University of Ulsan College of Medicine (República de Corea))
Wollner, M. (Rambam Health Care Campusm (Israel))
Hong, David (MD Anderson Cancer Center (Estats Units d'Amèrica))
Vogel, A. (Hannover Medical School (Alemanya))
Delmonte, A. (Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori)
Akimov, Mikhail (Novartis Pharma (Siïssa))
Ghebremariam, S. (Oncology Global Development-BDM)
Cui, X. (Novartis Institutes for Biomedical Research)
Nwana, N. (Oncology Precision Medicine)
Giovannini, M. (Novartis Pharmaceuticals Corporation(Estats Units d'Amèrica))
Kim, T. M. (Seoul National University Hospital)

Fecha:	2020
Resumen:	Dysregulation of receptor tyrosine kinase MET by various mechanisms occurs in 3%-4% of non-small-cell lung cancer (NSCLC) and is associated with unfavorable prognosis. While MET is a validated drug target in lung cancer, the best biomarker strategy for the enrichment of a susceptible patient population still remains to be defined. Towards this end we analyze here primary data from a phase I dose expansion study of the MET inhibitor capmatinib in patients with advanced MET-dysregulated NSCLC. Eligible patients [≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status ≤2] with MET-dysregulated advanced NSCLC, defined as either (i) MET status by immunohistochemistry (MET IHC) 2+ or 3+ or H-score ≥150, or MET/centromere ratio ≥2. 0 or gene copy number (GCN) ≥5, or (ii) epidermal growth factor receptor wild-type (EGFRwt) and centrally assessed MET IHC 3+, received capmatinib at the recommended dose of 400 mg (tablets) or 600 mg (capsules) b. i. d. The primary objective was to determine safety and tolerability; the key secondary objective was to explore antitumor activity. The exploratory end point was the correlation of clinical activity with different biomarker formats. Of 55 patients with advanced MET-dysregulated NSCLC, 40/55 (73%) had received two or more prior systemic therapies. All patients discontinued treatment, primarily due to disease progression (69. 1%). The median treatment duration was 10. 4 weeks. The overall response rate per RECIST was 20% (95% confidence interval, 10. 4-33. 0). In patients with MET GCN ≥6 (n = 15), the overall response rate by both the investigator and central assessments was 47%. The median progression-free survival per investigator for patients with MET GCN ≥6 was 9. 3 months (95% confidence interval, 3. 8-11. 9). Tumor responses were observed in all four patients with METex14. The most common toxicities were nausea (42%), peripheral edema (33%), and vomiting (31%). MET GCN ≥6 and/or METex14 are suited to predict clinical activity of capmatinib in patients with NSCLC ().
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Capmatinib ; MET amplification ; MET exon 14 ; MET mutation ; NSCLC
Publicado en:	Annals of oncology, Vol. 31 (march 2020) , p. 789-797, ISSN 1569-8041

DOI: 10.1016/j.annonc.2020.03.293
PMID: 32240796

0 p, 567.1 KB

El registro aparece en las colecciones:
Artículos > Artículos de investigación
Artículos > Artículos publicados