Masitinib is a tyrosine kinase inhibitor (TKI) licensed for treatment of non-resectable canine mast cell tumours; its major targets include c-kit, PDGFR and FAK kinases. Aberrant expression of c-kit and FAK have been found in human patients affected by cutaneous and mucosal melanoma. Masitinib and other TKIs with similar targets have been used in human patients with advanced stage melanoma bearing c-kit mutations with some encouraging results. The role of c-kit, FAK and PDGFR in canine melanoma has not been extensively investigated. Although c-kit mutation seems uncommon, strong c-kit expression has been found in around 50% of canine oral melanoma; however, correlation of c-kit mutation/expression with prognosis is still uncertain. PDGFR expression has been found in around 50% of oral canine melanoma and was shown to correlate with a worse prognosis in one study. The expression and importance of FAK in canine melanoma has not been reported yet.

The aim of this small study was to assess response rates and to a lesser extent survival, in advanced stage III and IV canine melanoma treated with masitinib, as a proof of concept that masitinib may potentially play a role in treatment of this disease.

Eleven dogs were prospectively enrolled, two with digital, one anal and eight oral melanoma. Only dogs with progressive gross disease despite conventional treatment were included in the study. All the dogs were staged with thoracic radiography and fine-needle aspirate of the regional lymph node when palpable. One dog had thoracic CT and abdominal ultrasound. All dogs had previously received various combinations of surgery, radiotherapy and melanoma vaccine treatment.

Two dogs achieved partial response, five dogs stable disease and four progressive disease. For all 11 dogs median TTP (time to tumour progression) and MST (median survival time) were 66 and 124 days, respectively. Masitinib was generally well tolerated with side effects only observed in three patients. One experienced grade 1 anaemia and neutropenia, one grade 2 anorexia and one grade 1 diarrhoea.

Mucosal melanoma is an aggressive disease that carries a poor prognosis, no effective systemic treatments are currently available to control the progression of metastatic disease. This small study showing some efficacy in end-stage disease, indicates that masitinib offers potential for treatment of canine melanoma. Further studies in earlier stage disease and possibly in combination with other modalities are needed to support our findings.

Disclosures

Disclosures to report
Masitinib tablets were donated by AB Science.