Margaret Von Mehren, MD

Dr. von Mehren discusses current considerations and challenges in the management of patients with soft tissue sarcoma, as well as recent clinical trial data.

Excellent safety, efficacy, and tolerability profiles have resulted in the rapid integration of oral tyrosine kinase inhibitors into most facets of the treatment of gastrointestinal stromal tumors (GIST).

Gastrointestinal stromal tumors have until recently had a uniformly poor prognosis with lack of effective drug therapies. These tumors usually have activating mutations in either KIT or PDGFR-α tyrosine kinase receptors. Over the past decade, imatinib (Gleevec), a selective tyrosine kinase inhibitor has become the standard of care for the first-line treatment of patients with unresectable and metastatic disease. For patients with imatinib-resistant disease or intolerant to the side effects of imatinib, sunitinib (Sutent), a multitargeted tyrosine kinase inhibitor was recently approved. For earlier-stage disease, status post–complete surgical excision, preliminary data seem encouraging for the role of adjuvant imatinib in prolonging patients' disease-free interval. The impact of neoadjuvant drug therapy needs to be further classified and explored. With additional evaluation of other tyrosine kinase inhibitors and novel therapies against other molecular markers, the treatment paradigm for this malignancy should continue to evolve.

We now have multiple novel agents that warrant testing in this disease setting. Clinical trials need not only test interesting drugs, but should also correlate information from tumor specimens and clinical responses.