Comprehensive genomic profiling aids in treatment of a metastatic endometrial cancer

FGFR-TACC fusions, including FGFR3-TACC3, have been identified as potential oncogenic drivers and actionable alterations in a number of different cancer types. The clinical relevance of FGFR3-TACC3 fusions in endometrial cancer has not yet been described. Formalin-fixed, paraffin-embedded metastatic endometrial carcinoma from the spleen and peritoneum were sent for comprehensive genomic profiling (CGP) using the FoundationOne platform as part of a prospective tumor genomic profiling protocol. We report the identification of an FGFR3-TACC3 fusion in a case of metastatic endometrioid endometrial cancer. Other potentially actionable alterations detected in this specimen included PIK3CA T1025S and an uncharacterized rearrangement involving TSC2. The patient initially received an FGFR inhibitor as an investigational agent and experienced stable disease with complete resolution of a pelvic nodule; however, treatment had to be discontinued because of intolerable side effects. A PET/CT scan nearly 3 mo after discontinuation showed disease progression. She subsequently received the mTOR inhibitor, temsirolimus, later accompanied by letrozole, and achieved stable disease. Clinical benefit was attributed to the mTOR inhibitor as tumor stained negative for estrogen receptor. Temsirolimus was discontinued after >17 mo because of disease progression. FGFR inhibitors may have clinical benefit in the treatment of endometrial carcinoma with FGFR3-TACC3 fusions. Additionally, clinical benefit from an mTOR inhibitor may reflect a response to targeting the alteration in PIK3CA or TSC2. More research is needed to understand the activity of FGFR3-TACC3 fusions on tumors and to discover additional therapeutic options for endometrial carcinoma patients with this gene fusion.