Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.

Abstract

Osteosarcoma is the most common pediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin. Moreover, studies have shown that auranofin significantly reduces pulmonary metastases in xenotransplant models.1 Here we describe a phase I/II study of auranofin in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single arm multicenter pilot study of auranofin in combination with standard-of-care (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical standard-of-care-only control group (n = 26). Dogs >15 kg received 9 mg auranofin q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3 year period. Auranofin plus standard-of-care improved overall survival (P = 0.036) in all dogs treated. The improved outcome was attributable entirely to improved overall survival in male dogs (P = 0.009). At the time of writing, ten dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that auranofin improves overall survival in male dogs when combined with standard-of-care. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery. This article is protected by copyright. All rights reserved.