Clinical application of the MEK inhibitor trametinib in dogs with oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a common and, if left untreated, deadly disease in dogs. The current standard of care involves wide-margin surgical excision of tumor tissue, which is frequently disfiguring. Surgical treatment can also be debilitating and lead to a reduced quality of life. Recent studies have demonstrated that OSCC in dogs typically shows highly elevated RAS signaling compared to healthy gingival tissue. Here, we examine the drug trametinib, which is FDA-approved for use in humans for BRAF-mutant melanomas, as an approach to treating OSCC in dogs. Domestic companion dogs (N = 20) with spontaneously occurring OSCC were recruited over a two-year period for an interventional study without concurrent controls. Dogs were prescribed 0.015 to 0.035 mg/kg trametinib daily to be given orally. Treatment was continued for 8 weeks, with examinations every 2 weeks. Health monitoring was conducted via routine bloodwork combined with at-home questionnaires. Tumor volume was assessed by caliper measurement and by computed tomography (CT) imaging. Tumor response categorization was based on R.E.C.I.S.T. criteria. Final R.E.C.I.S.T. categorization was based on CT measurement, while mid-experiment detection of progressive disease (PD) was based on caliper measurement. Dogs exited the study immediately upon determination of PD. Five dogs (25%) achieved a partial response (PR), and one dog (5%) had a complete response (CR) based on CT imaging at the end of 8 weeks of treatment, however cancer cells were detected by histological examination. Five dogs had stable disease (SD, 25%), and nine dogs (45%) were removed from the trial after demonstrating PD. For the seven dogs with BRAF p.V595E mutant tumors, one dog (14%) had PCR, four (57%) had PR, one (14%) had SD, and one (14%) had PD. Adverse events were rare, low grade, and resolved with outpatient supportive care. Trametinib blocks the growth of canine OSCC in approximately half of dogs, with objective response of 30% (CR+PR) and an additional 25% of dogs having SD. Overall, this work presents an effective, safe, and available targeted therapeutic approach for the treatment of OSCC tumors in dogs.