Histology-Specific Uses of Tyrosine Kinase Inhibitors in Non-gastrointestinal Stromal Tumor Sarcomas.

Adult sarcomas, especially those with metastatic or unresectable disease, have limited treatment options. Traditional chemotherapeutic options have been limited by poor response rates in patients with advanced sarcomas. The important clinical question is whether the success of targeted therapy in GIST can be extended to other sarcomas and also if preclinical data describing targets across this heterogeneous group of cancers can be translated to clinical efficacy of known and upcoming target specific agents. Multi-targeted tyrosine kinase inhibitors (TKI) such as pazopanib, sorafenib, sunutinib, cediranib have shown benefits across various histologies of soft tissue sarcoma as well as bone sarcomas. The efficacy of imatinib in Dermatofibrosarcoma Protruberans; sunitinib and cediranib in alveolar soft part sarcoma; and sorafenib and imatinib in chordomas have provided a treatment option of these rare tumors where no effective options existed. TKIs are being tested in combination with chemotherapy as well as radiation to improve response. Although traditional RECIST criteria may not adequately reflect response to these targeted agents, the studies have shown promise for the efficacy of TKIs across the spectrum of sarcomas. The integration of biomarker studies with clinical trials may help further identify responders beyond that defined by histology. With the current data, TKIs are being used both as first-line treatment and beyond in non-GIST sarcomas.

Current treatment options in oncology. 2016 Feb [Epub]

Tarsheen K Sethi, Vicki L Keedy

Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, 2220 Pierce Ave, 777 Preston Research Building, Nashville, TN, 37232-0001, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.., Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, 2220 Pierce Ave, 777 Preston Research Building, Nashville, TN, 37232-6307, USA. This email address is being protected from spambots. You need JavaScript enabled to view it..