Sunitinib Therapy for Melanoma Patients with KIT Mutations Clinical Cancer Research, 03/02/2012

Minor DR et al. – Sunitinib may have activity in patients with melanoma and KIT mutations; more study is needed. KIT mutations may represent an adverse prognostic factor in metastatic melanoma.

• Tumor tissues from 90 patients with stage III or IV acral, mucosal, or cumulative sun-damaged skin melanoma underwent sequencing of KIT, BRAF, NRAS, and GNAQ genes, FISH analysis for KIT amplification, and immunohistochemistry of KIT protein (CD117).
• Patients with mutations, amplifications, or overexpression of KIT were treated with sunitinib and responses measured by Response Evaluation Criteria in Solid Tumors (RECIST).

• Eleven percent of the melanomas tested had mutations in KIT, 23% in BRAF, 14% in NRAS, and none in GNAQ.
• Of 12 patients treated with sunitinib, 10 were evaluable.
• Of the 4 evaluable patients with KIT mutations, 1 had a complete remission for 15 months and 2 had partial responses (1- and 7-month duration).
• In contrast, only 1 of the 6 patients with only KIT amplification or overexpression alone had a partial response.
• In 1 responder with rectal melanoma who later progressed, the recurring tumor had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT.
• Interestingly, among patients with manifest stage IV disease, KIT mutations were associated with a significantly shortened survival time (P<0.0001).