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

Abstract

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.

Figure 1

CT chest images of pulmonary metastasis arising from anal melanoma at baseline (A) and then at 3 months (B) showing reduction in the size of the lesion on imatinib (Case 1).

Figure 2

CT pelvis and FDG PET/CT images at baseline (A, B) and at 1 month (C, D) after treatment of a metastatic vulval melanoma with imatinib. Arrows indicate areas of response (Case 2).

Figure 3

Marked LDH response within 2 weeks of commencing imatinib in a metastatic mucosal melanoma arising from the labia (Case 3). Dashed line indicates upper limit of the reference range.

Figure 4

Chest X-ray and chest CT images at baseline (A, B) and then at 1 month (C, D) after treatment of a metastatic anal melanoma with sorafenib demonstrates significant reduction in the number and size of pulmonary metastases. Arrows indicate major sites of response (Case 4).