BRAF and MEK Inhibitor Treatment for Metastatic Undifferentiated Sarcoma of the Spermatic Cord with BRAF V600E Mutation

Abstract An 18-year-old Japanese man was diagnosed with an undifferentiated sarcoma of the spermatic cord, with multiple distant metastases to the lungs and bones. The patient received doxorubicin-based standard chemotherapy. Although the chemotherapy was effective, it induced severe adverse events, which led to treatment discontinuation. A comprehensive genomic profiling test using resected tumor tissue revealed the BRAF V600E mutation. Based on the result, the patient received combination therapy with dabrafenib and trametinib. The combination therapy achieved a good response with few adverse events. However, 6.5 months later, pleural metastases and meningeal dissemination had emerged. A liquid comprehensive genomic profiling test was performed after the progression to identify the resistance mechanism, which resulted in the detection of no actionable gene alterations other than BRAF V600E. This report shows that the BRAF V600E mutation may be a promising therapeutic target and that resistance to the targeted therapy could also occur in soft tissue sarcoma. The significance of BRAF mutations across different types of cancer should be validated, and it is necessary to apply targeted therapies and develop methods to overcome resistance based on the optimal use of comprehensive genomic profiling tests.