Reference Detail

Ref Type

Journal Article

PMID

(20372153)

Authors

Handolias D, Hamilton AL, Salemi R, Tan A, Moodie K, Kerr L, Dobrovic A, McArthur GA

Title

Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT.

Journal	Vol	Issue	Date	Pages	Journal Short Title
British journal of cancer	102	8	2010 Apr 13	1219-23	Br J Cancer

URL

Abstract Text

Mutations in KIT are more frequent in specific melanoma subtypes, and response to KIT inhibition is likely to depend on the identified mutation.A total of 32 patients with metastatic acral or mucosal melanoma were screened for mutations in KIT exons 11, 13 and 17.KIT mutations were found in 38% of mucosal and in 6% of acral melanomas. Three patients were treated with imatinib and one with sorafenib. All four patients responded to treatment, but three have since progressed within the brain.The observed clinical responses support further investigation of KIT inhibitors in metastatic melanoma, selected according to KIT mutation status.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
KIT exon11	melanoma	predicted - sensitive	Imatinib	Case Reports/Case Series	Actionable	In a clinical case study, Gleevec (imatinib) treatment resulted in a partial response in a patient with metastastic anal melanoma harboring a 21 base-pair duplication in KIT exon 11, and reduced pulmonary metastasis by 60% (PMID: 20372153).	20372153
KIT K642E	vulvar melanoma	predicted - sensitive	Imatinib	Case Reports/Case Series	Actionable	In a clinical case study, Gleevec (imatinib) treatment resulted in partial response in a patient with recurrent vulval melanoma harboring KIT K642E, with reduction of tumor mass by 35% at 12 weeks (PMID: 20372153).	20372153
KIT L576P	melanoma	unknown	Imatinib	Case Reports/Case Series	Actionable	In a clinical case study, Gleevec (imatinib) treatment resulted in initial tumor reduction, but was followed by disease progression at all tumor sites in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153).	20372153
KIT D820Y	melanoma	predicted - sensitive	Sorafenib	Case Reports/Case Series	Actionable	In a clinical case study, Nexavar (sorafenib) treatment resulted in stable disease with 27% reduction in target lesions at 4 weeks in a patient with anal melanoma and pulmonary metastases harboring KIT D820Y (PMID: 20372153).	20372153