Background: Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel (micellar)) has shown promise in early‐phase studies. Hypothesis/Objectives: The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was μp = μL, (i.e. proportion of responders for the paclitaxel (micellar) and lomustine groups, respectively). Animals: Two hundred and fifty‐two dogs with advanced stage nonresectable grade 2 or 3 MCT. Methods: Prospective multicenter randomized double‐blind positive‐controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR) was also calculated. Safety was assessed through the characterization and grading of adverse events (AE). Results: Overall CORR (7% versus 1%; P = 0.048) and BORR (23% versus 10%; P = 0.012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar) treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty‐seven dogs (33%) receiving lomustine were discontinued due to hepatopathy compared to three (2%) receiving paclitaxel (micellar) (P < 0.0001; odds ratio 26.7). Conclusions/clinical importance: Paclitaxel (micellar)’s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.
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