Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skinстатья из журнала
Аннотация: Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities.We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Patients received imatinib 400 mg once per day or 400 mg twice per day if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening was performed by mass spectroscopy.Twenty-five patients were enrolled (24 evaluable). Eight patients (33%) had tumors with KIT mutations, 11 (46%) with KIT amplifications, and five (21%) with both. Median follow-up was 10.6 months (range, 3.7 to 27.1 months). Best overall response rate (BORR) was 29% (21% excluding nonconfirmed responses) with a two-stage 95% CI of 13% to 51%. BORR was significantly greater than the hypothesized null of 5% and statistically significantly different by mutation status (7 of 13 or 54% KIT mutated v 0% KIT amplified only). There were no statistical differences in rates of progression or survival by mutation status or by melanoma site. The overall disease control rate was 50% but varied significantly by KIT mutation status (77% mutated v 18% amplified). Four patients harbored pretreatment NRAS mutations, and one patient acquired increased KIT amplification after treatment.Melanomas that arise on mucosal, acral, or CSD skin should be assessed for KIT mutations. Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib.
Год издания: 2013
Авторы: F. Stephen Hodi, Christopher L. Corless, Anita Giobbie‐Hurder, Jonathan A. Fletcher, Meijun Zhu, Adrián Mariño‐Enríquez, Philip Friedlander, René González, Jeffrey S. Weber, Thomas F. Gajewski, Steven O’Day, Kevin B. Kim, Donald P. Lawrence, Keith T. Flaherty, Jason J. Luke, Frances A. Collichio, Marc S. Ernstoff, Michael C. Heinrich, Carol Beadling, Katherine Zukotynski, Jeffrey T. Yap, Annick D. Van den Abbeele, George D. Demetri, David E. Fisher
Издательство: Lippincott Williams & Wilkins
Источник: Journal of Clinical Oncology
Ключевые слова: Cutaneous Melanoma Detection and Management, Sarcoma Diagnosis and Treatment, CAR-T cell therapy research
Другие ссылки: Journal of Clinical Oncology (PDF)
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Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Journal of Clinical Oncology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 31
Выпуск: 26
Страницы: 3182–3190