Abstract
Soft tissue sarcoma represents about 1% of all solid malignancies. The standard chemotherapy regimens have included doxorubicin alone or in combination with other agents. Despite recent advances in treatment beyond first line - with the FDA approval of pazopanib, eribulin and trabectidin - overall survival for patients with metastatic disease remains in the region of 12-19 months. Olaratumab is a monoclonal antibody directed against platelet-derived growth factor receptor alpha (PDGFRalpha). It was studied in a phase Ib and randomized phase II study in combination with doxorubicin in patients with soft tissue sarcoma who previously had not received doxorubicin for metastatic disease. The results of the phase II study showed a statistically significant improvement in progression-free survival up to 6 months, and a more dramatic improvement in overall survival to 26.9 months. This is the first randomized trial to show a significant improvement in overall survival compared to doxorubicin alone. An ongoing phase III study has completed accrual and results are being analyzed. Olaratumab has been granted accelerated approval by the United States Food and Drug Administration. Ongoing trials are underway to further demonstrate the mechanism of action. This review will document the studies involved in the development of olaratumab in the treatment of soft tissue sarcomas.
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