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Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors

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  • 1 Gulf Coast Veterinary Specialists, 1111 W Loop S Freeway, Houston, TX 77027.
  • | 2 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37919.
  • | 3 Florida Veterinary Specialists and Cancer Treatment Center, 3000 Busch Lake Blvd, Tampa, FL 33614.
  • | 4 Veterinary Specialty Hospital, 10435 Sorrento Valley Rd, San Diego, CA 92121.
  • | 5 California Veterinary Specialists Angel Care Cancer Center, 2310 Faraday Ave, Carlsbad, CA 92008.
  • | 6 MedVet Associates Limited, 300 E Wilson Bridge Rd, Worthington, OH 43085.
  • | 7 East Bay Veterinary Specialists, 2803 Ygnacio Valley Rd, Walnut Creek, CA 94598.
  • | 8 Veterinary Cancer Associates PA, 1111 W Loop S Freeway, Houston, TX 77027.
  • | 9 Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 10 Southeast Veterinary Oncology, 304 Corporate Way, Orange Park, FL 32073.
  • | 11 Animal Clinical Investigation at Friendship Hospital for Animals, 4105 Brandywine St NW, Washington, DC 20016.
  • | 12 Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215.
  • | 13 Inserm UMR 891, Centre de Recherche en Cancérologie de Marseille, 27 Blvd Lei Roure, 13009 Marseille, France.
  • | 14 AB Science Société Anonyme, 3 Ave George V, 75008 Paris, France.
  • | 15 AB Science Société Anonyme, 3 Ave George V, 75008 Paris, France.
  • | 16 CNRS UMR 8147, Service d'hématologie, Centre de référence des mastocytoses, Hôpital Necker, Université Paris Descartes, 149 Rue de Sèvres, 75015 Paris, France.

Abstract

Objective—To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment.

Animals—132 dogs with nonresectable grade 2 or 3 MCTs.

Procedures—Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time.

Results—In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib.

Conclusions and Clinical Relevance—Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.

Abstract

Objective—To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment.

Animals—132 dogs with nonresectable grade 2 or 3 MCTs.

Procedures—Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time.

Results—In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib.

Conclusions and Clinical Relevance—Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.

Contributor Notes

Dr. Hahn's present address is Hill's Pet Nutrition Incorporated, 1035 NE 43rd St, Topeka, KS 66617.

The authors thank Drs. Monika Jankowski, Stephanie Correa, Robyn Elmslie, Patrick Devauchelle, Didier Lanore, Craig Clifford, Ruthanne Chun, Rodney Ayl, Ronald Burk, Cheryl London, Cheryl Harris, Gerald Post, Dominique Heripret, and Claude Muller for assistance with treatment of dogs with mast cell tumors and Dr. Candice Drouin for technical assistance.

Address correspondence to Dr. Hahn (kevin_hahn@hillspet.com).