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The routine use of next-generation sequencing in multiple solid tumors has allowed oncologists to identify actionable genomic alterations, including RAS, BRAF, and PIK3CA mutations in colorectal cancer. Studies also suggest that rare oncogenic gene fusions, seen in less than 1% of patients, may define unique molecular subsets that could provide even more actionable targets.
To date, investigations of rearranged during transfection (RET) gene fusions and the use of the selective RET inhibitors selpercatinib (Retevmo) and pralsetinib (Gavreto) have demonstrated high efficacy in patients with RET-driven non–small cell lung cancer and thyroid cancers, for example. The authors of a new case report in JCO Precision Oncology have now described a clinically meaningful response with the use of selpercatinib in a 54-year-old woman with metastatic colorectal cancer harboring a RET-NCOA4 fusion -- one of the most frequent RET rearrangements -- as well as a RAD50 mutation.
"The patient achieved a durable response to first-line platinum-based chemotherapy, followed by disease control with selpercatinib and subsequent surgical resection of a resistant hepatic metastasis," wrote Giovanni Trovato, MD, and other colleagues at IRCCS Comprehensive Cancer Center in Rome, Italy. "This case illustrates the relevance of comprehensive genomic profiling (CGP) in colorectal cancer and highlights potential therapeutic and biological implications of RET fusions and RAD50 mutations."
