Introduction

The FidoCure® platform integrates canine tumor genomics with access to small molecule, targeted therapeutics. The use of small molecule inhibitors (SMIs), given their success in treating cancers in people, is an attractive therapeutic opportunity in canine cancer. The purpose of this investigation was to evaluate the adverse event profile of 8 SMIs (trametinib, rapamycin, lapatinib, dasatinib, imatinib, vorinostat, toceranib and crizotinib) in tumor- bearing canine patients enrolled through FidoCure®.

Methods

Proposed initial doses for these SMIs were gleaned from the veterinary literature (i.e., imatinib, rapamycin, dasatinib, vorinostat and toceranib) or from the respective drug’s FDA and/or EMA approval package’s NOAEL established for normal dogs. Adverse events (AEs) were collected from patient clinical records and graded mild, moderate, or severe based upon clinical characteristics including degree of therapeutic intervention required for resolution, changes to quality of life, and adjustment to dose or interval of the targeted therapy.

Results

Of 464 patients with clinician reported outcomes, 156 patients (34%) reported a suspected adverse event. Across all agents, AEs were predominantly mild (61%) with only 4 AEs graded as severe. Many of these pets were treated with a combination of cytotoxic chemotherapy and SMIs. The most commonly reported adverse events include lethargy, anorexia, vomiting, diarrhea, anemia, and/or liver enzyme elevation.

Conclusion

The adverse event profiles of the SMIs enabled by FidoCure are comparable to previously published reports of the safety of Palladia® used alone or in combination with cytotoxic chemotherapy. Studies categorizing results according to the VCOG-CTCAE criteria and research evaluating the PK and PD of these drugs are underway.