Systematic Review of Recurrent Osteosarcoma Systemic Therapy

SIMPLE SUMMARY: Osteosarcoma is the most common primary bone cancer. Its therapeutic approach includes cytotoxic chemotherapy and surgery. However, when recurrence or metastasis occurs the therapeutic options are limited with poor results. Herein we have conducted a systematic review of the systemic treatment options in recurrent and/or metastatic osteosarcoma over the last two decades. Our results indicate the paucity of our therapeutic armamentarium for this entity, with the majority of the studied modalities resulting in limited or no benefits. Intense translational research and future clinical studies reveal the unmet need for new treatment options for osteosarcoma patients with metastatic and/or recurrent disease. ABSTRACT: Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.