Metastatic vulvar melanoma is a rare and aggressive disease and survival is 
usually poor. Vulvar melanomas harbor BRAF V600 mutations only infrequently; 
consequently, target therapy is a rare therapeutic option and immunotherapy 
usually has only a weak effect. On the other hand, KIT mutations are rare in 
cutaneous melanomas, but relatively frequent in mucosal melanomas, particularly 
in vulvar-vaginal melanomas, and can be a therapeutic target. Herein, we report 
a clinical case of a patient with metastatic vulvar melanoma, harboring an exon 
17 c-KIT mutation, treated with avapritinib (BLU-285) - a highly potent and 
selective oral kinase inhibitor designed to treat imatinib-resistant 
gastro-intestinal stromal tumors (GIST) by targeting KIT/PDGFRα activation loop 
mutants (exons 17/18). After failure of the combination of 
ipilimumab + nivolumab first and then nivolumab alone, the patient received 
avapritinib 300 mg/daily for central nervous system (CNS), lymph-nodal, right 
adrenal gland, lung, and subcutaneous metastases. Best response was partial 
remission, according to RECIST 1.1 criteria. Time to treatment progression was 
11 months. Main toxicities were grade 2 cutaneous vasculitis that required 
avapritinib discontinuation, and grade 2 uveitis of unknown origin, treated by 
vitrectomy and empiric antibiotic and antiviral therapy due to negative cultural 
tests. Uveitis was detected at the time of progression and therapy was 
definitively discontinued. In conclusion, avapritinib proved to be effective 
even in the presence of a pretreated disease, a high tumor burden, and brain 
metastases. In our experience, treatment was feasible and toxicity manageable. 
Considering the lack of effective therapies and the poor outcome of the disease, 
determination of c-KIT mutations should be performed routinely in cases of 
metastatic mucosal melanoma.