Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Abstract

BackgroundGastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High‐risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting.ObjectivesTo review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value.AnimalsTwenty‐seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib.MethodsRetrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs.ResultsFive of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression‐free interval (PFI) in dogs with gross disease was 110 weeks (range, 36‐155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9‐257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib‐treated dogs.Conclusions and Clinical ImportanceBiological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib‐treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

“…Toceranib is a multitargeted TKI targeting several RTKs, including VEGFR, PDGFR, KIT, CSF1R, and FLT3 and was developed as an orally bioavailable anti‐angiogenic drug . While it was approved for the treatment of canine mast cell tumours owing to its KIT inhibitory properties, toceranib has demonstrated activity against other solid histologies, including sarcomas and carcinomas . Its clinical utility remains unclear based on several recent studies.…”

“…Its clinical utility remains unclear based on several recent studies. A recent retrospective evaluation of dogs with GISTs treated with toceranib documented objective response (complete or partial response) in 4/7 dogs with measurable disease, suggesting efficacy in this specific tumour type . However, other studies have failed to show a clear clinical benefit.…”

“…186,187 While it was approved for the treatment of canine mast cell tumours owing to its KIT inhibitory properties, toceranib has demonstrated activity against other solid histologies, including sarcomas and carcinomas. 36,38,186,187 Its clinical utility remains unclear based on several recent studies. A recent retrospective evaluation of dogs with GISTs treated with toceranib documented objective response (complete or partial response) in 4/7 dogs with measurable disease, suggesting efficacy in this specific tumour type.…”

“…A recent retrospective evaluation of dogs with GISTs treated with toceranib documented objective response (complete or partial response) in 4/7 dogs with measurable disease, suggesting efficacy in this specific tumour type. 38 However, other studies have failed to show a clear clinical benefit. A randomized, prospective clinical trial of dogs with appendicular osteosarcoma in which dogs received metronomic cyclophosphamide/piroxicam with or without toceranib following standard of care therapy (amputation and carboplatin chemotherapy) found no significant difference in disease-free interval, OS or 1-year survival rate.…”

CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies

“…According to a recent report from the National Academy of Medicine (64), only one out of ten oncology candidates that appear promising in preclinical mouse models are in fact effective and safe in human clinical trials. This overtly high attrition rate highlights the need for alternative models at the early stage of the Drug Research and Development lifecycle (65), as shown in other therapeutic areas (66)(67)(68)(69)(70)(71).…”