{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:34:32Z","timestamp":1791729272956,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2012,5,17]],"date-time":"2012-05-17T00:00:00Z","timestamp":1337212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Microphthalmia transcription factor (MITF)\u2010associated (MiT) tumors are a family of rare malignancies, including alveolar soft part sarcoma (ASPS), clear cell sarcoma (CCS), and translocation\u2010associated renal cell carcinoma (tRCC) that have dysregulated expression of oncogenic MITF family proteins. The MET receptor tyrosine kinase gene is transcriptionally activated by MITF family proteins, making MET a potential therapeutic target for MiT tumors. This study assessed the activity of tivantinib (ARQ 197), a selective MET inhibitor, in patients with MiT\u2010associated tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>This multicenter, single\u2010arm, phase 2 trial enrolled patients with advanced MiT tumors. Patients initially received tivantinib 120 mg orally twice daily, then 360 mg twice daily per protocol amendment. The primary endpoint was overall response rate. Secondary endpoints included safety, progression\u2010free survival, pharmacokinetics, and correlative studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>A total of 47 patients (median age, 25 years; range, 11\u201073 years) with ASPS (n = 27), CCS (n = 11), tRCC (n = 6), or other tumor types (n = 3) were enrolled. Common grade 3\/4 drug\u2010related adverse events included anemia (4%) and neutropenia (4%). Three patients (6.4%) experienced 4 treatment\u2010related serious adverse events (grade 3 febrile neutropenia, thrombocytopenia, and deep vein thrombosis, and grade 4 thrombocytopenia). Best response was partial response in 1 CCS patient (2%) and stable disease in 28 patients (60%). Median progression\u2010free survival was 3.6 months (overall), 5.5 months (ASPS), and 1.9 months (CCS and tRCC). Baseline MET expression was strongly or focally positive in tumor samples from 14 of 19 patients (74%).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Tivantinib was safe and tolerable in patients with MiT tumors, but antitumor activity was modest. Cancer 2012. \u00a9 2012 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.27582","type":"journal-article","created":{"date-parts":[[2012,5,17]],"date-time":"2012-05-17T16:04:32Z","timestamp":1337270672000},"page":"5894-5902","source":"Crossref","is-referenced-by-count":138,"title":["Tivantinib (ARQ 197), a selective inhibitor of MET, in patients with microphthalmia transcription factor\u2013associated tumors"],"prefix":"10.1002","volume":"118","author":[{"given":"Andrew J.","family":"Wagner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven 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