A precision medicine approach in sarcoma: identification of patients who may benefit from early use of pazopanib

Abstract

Soft tissue sarcomas (STS) are a heterogeneous group of over 100 histologically and genetically distinct mesenchymal tumors. Standard of care for metastatic STS has historically relied on anthracycline-based chemotherapy regimens. Although effective for some patients, conventional chemotherapeutic agents used in STS are associated with substantial toxicity and also are not equally effective in all histologic subtypes of sarcoma. Pazopanib is an orally active antiangiogenic drug that is approved for non-adipogenic sarcomas after failure of at least one line of previous chemotherapy, and has a relatively favorable toxicity profile. Earlier use of pazopanib may be a better choice for patients with subtypes of sarcoma that do not respond well to conventional chemotherapy or those who are unlikely to tolerate chemotherapy. Here we review the evidence for the activity and toxicity profile of pazopanib and consider potential histologic, clinical, and genetic predictive factors that can help to guide treatment choices. Further prospective studies validating these observations may lead to refinement of a precision medicine approach to match ideal sarcoma patients to earlier treatment with pazopanib over traditional chemotherapy.