Reference Detail

Ref Type

Journal Article

PMID

(35820244)

Authors

Corti C, Conforti F, Pala L, Catania C, Cocorocchio E, Ferrucci PF, Curigliano G, Queirolo P, de Pas T

Title

Differential activity of avapritinib in patients with metastases from mucosal melanoma and thymic carcinoma harbouring KIT exon 17 mutations: Initial experience from a Compassionate Use Program in Italy.

Journal	Vol	Issue	Date	Pages	Journal Short Title
European journal of cancer (Oxford, England : 1990)	172		2022 Jul 09	332-339	Eur J Cancer

URL

Abstract Text

Proto-oncogene KIT is the gene encoding the receptor tyrosine kinase protein KIT. Activating mutations are found in 2.9% of neoplasms, with the highest prevalence in gastrointestinal stromal tumour. Exon 17 mutations typically alter the kinase activation loop and are relatively rare, representing 11.7% of all activating KIT mutations. Recently, KIT exon 17 mutants turned out to be a potential molecular target for the type 1 kinase inhibitor avapritinib (BLU-285).In this framework, we aimed at investigating the potential activity of avapritinib in mucosal melanoma and thymic carcinoma, two disease histologies with dismal prognosis, currently lacking evidence-based second line treatment options and in which KIT exon 17 activating mutations could represent a relevant therapeutic target.In this series, we report the only four cases of patients affected by exon 17 mutant mucosal melanoma and thymic carcinoma that have been treated in Italy with avapritinib within a Compassionate Use Program. Two patients harboured mucosal melanoma and the other two were diagnosed with thymic carcinoma. We describe a differential activity of avapritinib (3/4 patients responded, 1/4 did not respond), along with possible hypotheses to justify such differences and potential implications for precision oncology.Taken together, the inactivity of imatinib on KIT exon 17 mutations, the general low clinical efficacy of immunotherapy, as well as the consequent formal lack of standard available and active second line systemic treatments in both mucosal melanoma and thymic carcinoma, support the implementation of avapritinib in the therapeutic armamentarium, even though further prospective evidence is warranted.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
KIT N822K	mucosal melanoma	predicted - sensitive	Avapritinib	Case Reports/Case Series	Actionable	In a clinical case study, Ayvakit (avapritinib) resulted in a partial response in extracranial lesions and stable disease in the central nervous lesions that lasted for 11 months in a patient with mucosal melanoma harboring KIT N822K (PMID: 35820244).	35820244
KIT exon17	mucosal melanoma	predicted - sensitive	Avapritinib	Case Reports/Case Series	Actionable	In a clinical case study, Ayvakit (avapritinib) resulted in a reduction of the metastatic lesions, including brain metastases, in a patient with mucosal melanoma harboring a KIT exon 17 mutation (PMID: 35820244).	35820244
KIT N822K	thymus squamous cell carcinoma	predicted - sensitive	Avapritinib	Case Reports/Case Series	Actionable	In a clinical case study, Ayvakit (avapritinib) resulted in stable disease in a patient with thymus squamous cell carcinoma harboring KIT N822K (PMID: 35820244).	35820244