Clinical response of masitinib mesylate in the treatment of canine macroscopic mast cell tumours

Lanoré, D.

doi:10.1111/jsap.12480

Cited by 15 publications

(19 citation statements)

References 31 publications

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“…In this case series, including dogs with advanced staged disease, the initial response to TKIs was the most significant prognostic factor, as previously reported by Smrkovski et al ( 27 ) and Grant et al ( 34 ). In contrast, histological grade, mitotic index, Ki-67 value, KITr pattern and even the mutational status in exon 11 of the c-kit oncogene had no impact on OS for these subjects.…”

Section: Discussionsupporting

confidence: 83%

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high‑risk canine mast cell tumours to tyrosine kinase inhibitors

et al. 2017

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The aim of the present prospective-retrospective study was to evaluate the response of high-risk canine mast cell tumours (MCTs) to tyrosine kinase inhibitors (TKIs) and to correlate this with prognostic factors. A total of 24 dogs presented with macroscopic cutaneous MCTs at disease stage II or III, and therefore, at high-risk of associated mortality, were included in the study and treated with masitinib (n=20) or toceranib (n=4). A total of 12/24 dogs achieved an objective response and the overall survival (OS) for all subjects was 113 days. Dogs responding to treatment had a significant increase in OS compared to non-responders (146.5 days vs. 47 days, P=0.02). Internal tandem duplications in exon 11 of the c-kit gene were identified in 6/24 cases. Ki67, KIT immunolabelling and c-kit mutation did not provide information regarding prognosis or prediction of response to TKIs in this population. Initial response to TKIs appears to be the most reliable prognostic factor for survival duration.

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Section: Discussionsupporting

confidence: 83%

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high‑risk canine mast cell tumours to tyrosine kinase inhibitors

et al. 2017

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“…Recently, the use of tyrosine kinase inhibitors (TKIs) has become more prevalent in veterinary medicine and appears to be effective in the treatment of MCTs in dogs . In a placebo‐controlled trial of toceranib phosphate, a TKI that targets Kit mutations in canine MCTs, a response rate nearing 70% was observed in tumours that possessed the c‐kit mutation, and dogs treated with toceranib achieved a significantly longer time to progression as compared to the placebo‐treated dogs .…”

Section: Introductionmentioning

confidence: 99%

Association of prognostic features and treatment on survival time of dogs with systemic mastocytosis: A retrospective analysis of 40 dogs

Moirano

Lima

Hume

et al. 2017

Vet Comparative Oncology

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Systemic mastocytosis is a rare phenomenon, with limited information regarding prognostic features and effective treatment of canine patients with this disease. The objective of this study is to determine the impact of certain features and treatments on dogs with systemic mastocytosis. The medical records of 40 dogs from 4 northeastern US veterinary hospitals, with evidence of systemic mast cell disease, were evaluated retrospectively. Variables analysed with relation to overall survival and prognostic significance included treatment protocol used, substage, presence of a cutaneous or visceral tumour, presence of multiple cutaneous Mast cell tumours, grade of the primary tumour and metastatic site(s). Dogs with metastatic disease confined to distant lymph nodes lived longer than those with circulating mast cells in the blood (P = .001), and those with metastatic disease evident in more than 2 sites had a worse prognosis than those with disease in a single location (P = .005). Additionally, administration of chemotherapeutic agents led to increased survival over prednisone therapy alone (P = .008), with the combination of lomustine, vinblastine and prednisone prolonging survival over the tyrosine kinase inhibitor, toceranib phosphate (P = .002). Presence of mast cells in the blood and/or evidence of disease in more than 2 sites indicate widespread dissemination suggesting their use as negative prognostic features. Furthermore, a chemotherapy protocol including combination lomustine and vinblastine therapy may be more effective than toceranib phosphate for the treatment of dogs with disseminated mast cell disease. Overall, patients with systemic mastocytosis have a grave prognosis and more effective treatment options are needed.

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“…In both studies, objective response rates (ORR) were approximately 40%, and tumors with c‐kit activating mutations had an increased ORR. A more recent retrospective study of masitinib in dogs with macroscopic MCT reported an ORR of 82%; neither KIT localization nor c‐kit mutation status was assessed in these tumors …”

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confidence: 96%

“…A more recent retrospective study of masitinib in dogs with macroscopic MCT reported an ORR of 82%; neither KIT localization nor c-kit mutation status was assessed in these tumors. 13 KIT subcellular localization has been evaluated by immunohistochemistry (IHC), and a correlation between aberrant KIT localization and activating mutations was found. 3 This finding is presumably due to activated KIT molecules being removed from the cell membrane and internalized more rapidly than inactivated KIT.…”

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confidence: 99%

c‐Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine

Weishaar

Ehrhart

Avery

et al. 2017

Veterinary Internal Medicne

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Background KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c‐kit mutations.Hypothesis/ObjectivesTo determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c‐kit mutated MCT would have a better response to TOC than VBL.AnimalsEighty‐eight client‐owned dogs with macroscopic MCT.MethodsProspective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m2 weekly × 4 then EOW) by KIT localization and c‐kit mutation status using an adaptive randomization scheme.ResultsSixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c‐kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62–3.92]; P = 0.28). Median progression‐free survival (PFS) for dogs receiving VBL was 78 days (7–1,521) and for TOC 95.5 (14–990); hazard ratio (HR) = 1.34 [0.72–2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10–1,521) for the VBL group and 159 (20–990) for the TOC group; HR = 0.80 ([0.45–1.41]; P = 0.44).Conclusions and Clinical ImportanceNeither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c‐kit mutations was not different between treatment groups in this population of dogs, c‐kit mutation status did not predict treatment response.

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Clinical response of masitinib mesylate in the treatment of canine macroscopic mast cell tumours

Abstract: Masitinib appears to be a well-tolerated and effective drug against macroscopic mast cell tumours.

Cited by 15 publications

References 31 publications

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high‑risk canine mast cell tumours to tyrosine kinase inhibitors

Clinical, histological, immunohistochemical and genetic factors associated with measurable response of high‑risk canine mast cell tumours to tyrosine kinase inhibitors

Association of prognostic features and treatment on survival time of dogs with systemic mastocytosis: A retrospective analysis of 40 dogs

c‐Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine

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