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Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib

Wang, Samantha X.Y.a; Zhang, Bing M.b; Wakelee, Heather A.a; Koontz, Michael Z.d; Pan, MingGuie; Diehn, Maximilianc; Kunder, Christian A.b; Neal, Joel W.a

doi: 10.1097/CAD.0000000000000765

The mesenchymal-to-epithelial transition (MET) gene is altered and becomes a driver mutation in up to 5% of non-small-cell lung cancer (NSCLC). We report our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including responses to the MET inhibitors crizotinib and cabozantinib. We identified cases of NSCLC with METex14 mutations using an institutionally developed or commercial next-generation sequencing assay. We assessed patient and disease characteristics by retrospective chart review. Some patients were treated off-label by the physician with crizotinib or cabozantinib, and tumor responses to these agents were assessed. A total of 15 patients with METex14-mutated NSCLC were identified, predominantly male (n=10) with a smoking history (60%) and a median age of 74.0 years. No other actionable somatic mutations were detected. Stage distribution included 26.7% stage I, 6.7% stage II, 6.7% stage III, and 60.0% stage IV. Among patients treated with crizotinib or cabozantinib (n=6), three patients showed partial response and one patient showed stable disease on the basis of RECIST criteria. Four patients experienced side effects requiring drug holiday, reduction, or cessation. Our findings highlight the diversity in presentation and histology of NSCLC with METex14 mutations, which were found in the absence of other actionable driver mutations. We observed evidence of tumor response to crizotinib and cabozantinib, supporting the previous reports that METex14 mutations in NSCLC are actionable driver events.

Departments of aMedicine, Division of Oncology


cRadiation Oncology, Stanford University School of Medicine, Stanford

dPacific Cancer Care, Monterey

eKaiser Permanente, Santa Clara, California, USA

Correspondence to Joel W. Neal, MD, PhD, Stanford Cancer Institute, 875 Blake Wilbur Drive, CC 2220, MC 5826, Stanford, CA 94305, USA Tel: +1 650 725 3081; fax: +1 650 498 5800; e-mail:

Received June 15, 2018

Accepted January 24, 2019

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