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c-Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and
K M Weishaar1, E J Ehrhart2, A C Avery2
1Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Fort Collins, CO.
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/Objectives:
To 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.
Animals:
Eighty-eight client-owned dogs with macroscopic MCT.
Methods:
Prospective, 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.
Results:
Sixty 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 Importance:
Neither 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.
Insights
Toceranib (TOC) and vinblastine (VBL) showed similar efficacy in treating canine mast cell tumors (MCTs). KIT genotyping did not predict treatment response, indicating c-kit mutation status is not a reliable factor for selecting between TOC or VBL.
Area of Science:
- Veterinary Oncology
- Comparative Oncology
- Canine Cancer Research
Background:
- Macroscopic mast cell tumors (MCTs) are common in dogs.
- Toceranib (TOC), a KIT inhibitor, and vinblastine (VBL) are used for MCT treatment.
- Prospective comparisons and the role of c-kit mutations in treatment selection are unclear.
Purpose of the Study:
- To evaluate KIT genotyping and localization for guiding treatment decisions in canine MCT.
- To compare the efficacy of TOC versus VBL in dogs with macroscopic MCT.
- To test the hypothesis that c-kit mutated MCT would respond better to TOC than VBL.
Main Methods:
- Eighty-eight dogs with macroscopic MCT participated in a prospective, randomized trial.
- Dogs were assigned to TOC or VBL based on KIT localization and c-kit mutation status.
- An adaptive randomization scheme was employed to allocate treatments.
Main Results:
- Sixty dogs received TOC and 28 received VBL; c-kit mutation prevalence was similar between groups (20% TOC vs. 30% VBL).
- Overall response rates were 46% for TOC and 30% for VBL (not statistically significant).
- Median progression-free survival and overall survival did not differ significantly between the TOC and VBL groups.
Conclusions:
- Neither TOC nor VBL demonstrated superior efficacy in terms of progression-free survival or overall survival for macroscopic MCT.
- KIT mutation status did not predict treatment response in this study population.
- Current findings suggest c-kit mutation status is not a reliable biomarker for selecting between TOC and VBL for canine MCT.
