Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT
D Handolias, AL Hamilton, R Salemi, A Tan, K Moodie, L Kerr, A Dobrovic, GA McArthur
BRITISH JOURNAL OF CANCER | NATURE PUBLISHING GROUP | Published : 2010
BACKGROUND: Mutations in KIT are more frequent in specific melanoma subtypes, and response to KIT inhibition is likely to depend on the identified mutation. METHODS: A total of 32 patients with metastatic acral or mucosal melanoma were screened for mutations in KIT exons 11, 13 and 17. RESULTS: 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. CONCLUSION: The observed clinical responses support further investigation of KIT inhibitors in metastatic melanoma, selected according to KIT mutation status.
We thank Novartis for their financial support, Victoria Beshay for mutation screening, Boris Bastian, Glenn Lynch and Petranel Ferrao for discussion and Jill Magee, Chris Angel and Graham Mason for their pathology input. Thanks to Kathryn Kinross for assistance with images. This work was supported by grants from the NHMRC and a Sir Edward Dunlop Clinical Research Fellowship from the Cancer Council of Victoria (GA McArthur) and an Australian Postgraduate Award from the University of Melbourne (D Handolias).