Durable Response to Selpercatinib in Metastatic Colorectal Cancer Harboring a Novel TIMM23B::RET Fusion: A Case Report

RET fusions are rare but actionable oncogenic drivers in metastatic colorectal cancer (mCRC), occurring in a small molecular subset with limited clinical evidence for selective RET inhibition. We report a 77-year-old woman with mCRC harboring a rare TIMM23B::RET fusion who achieved durable benefit from selpercatinib after progression on capecitabine. Molecular profiling showed RAS/BRAF wild-type, microsatellite-stable disease with a TIMM23B::RET fusion. Selpercatinib induced a marked decline in tumor markers and a sustained partial response on serial imaging. Treatment was complicated by grade 3 hepatotoxicity, requiring temporary interruption and dose reduction to 80 mg twice daily. Despite this, disease control was maintained without further grade ≥ 3 toxicity. At the time of writing, the patient remains on treatment with progression-free survival exceeding 14 months. To our knowledge, this is among the first detailed reports of mCRC harboring a TIMM23B::RET fusion with documented clinical benefit from selpercatinib. This case highlights the value of comprehensive genomic profiling and individualized toxicity management in rare molecular subsets of mCRC.