Sunitinib Therapy for Melanoma Patients with KIT Mutations
Menée sur 10 patients atteints de mélanome, cette étude évalue l'association entre la présence d'une mutation, d'une amplification ou surexpression du gène KIT et la réponse à un traitement par sunitinib
Purpose: Recent studies have shown activating KIT mutations in melanoma originating from mucosa, acral, or cumulative sun-damaged skin (CSDS) sites. We aimed to assess the predictive role of KIT mutation, amplification, or overexpression for response to treatment with the kinase inhibitor sunitinib. Experimental design: Tumor tissues from 90 patients with stage III or IV acral, mucosal, or CSDS 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 RECIST criteria. Results: 11% 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 four evaluable patients with KIT mutations, one had a complete remission for 15 months and two had partial responses (1 and 7 months duration). By contrast, only one of the six patients with only KIT amplification or overexpression alone had a partial response. In one 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). Conclusions: Sunitinib may have activity in melanoma patients with KIT mutations; more study is needed. KIT mutation may represent an adverse prognostic factor in metastatic melanoma.
Clinical Cancer Research , résumé, 2012