Exceptional Clinical Response to BRAF-Targeted Therapy in a Patient with Metastatic Sarcoma

Abstract

Soft tissue sarcomas (STS) are a rare and heterogeneous group of tumors arising from mesenchymal tissue comprising 1% of all adult cancers. The prognosis of metastatic STS is dismal. As there are few active drugs, there is a critical need to find new therapeutic alternatives in order to improve outcomes.

Most sarcoma subtypes are fairly resistant to standard chemotherapy regimens and/or have a short duration of response. The era of molecular targeted therapy may present new treatment options for metastatic STS and an opportunity to drive biomarker discovery and personalized medicine.

This case report describes a patient with a synchronous metastatic high-grade sarcoma who was treated with BRAF-targeted therapy with resolution of his metastatic lesions. To our knowledge, this exceptional response has not been described in sarcoma literature.

The patient presented with a large anterior abdominopelvic wall mass. Biopsy showed a high-grade spindle cell sarcoma. Staging scans confirmed two pulmonary metastases.

He was initiated on combination chemotherapy with mixed results. He received 50 Gy of radiation to the primary tumor followed by two additional cycles of combination chemotherapy, with an interval increase in the size of the pulmonary metastases. 

Molecular testing revealed a BRAF V600E mutation in the primary tumor. The patient was initiated on dabrafenib/trametinib with a dramatic response and resolution of his pulmonary metastases. The patient underwent surgical resection of his primary mass, and pathology confirmed no evidence of residual disease. 

Detailed genetic characterization of STS coupled with novel therapeutic strategies, including molecular targeted therapy, may have the potential to transform the care of patients diagnosed with sarcoma.