Gastrointestinal (GI) malignancies such as pancreatic and colorectal cancers (CRCs) are difficult to treat, some of which have poor response to standard of care. Emergence of next-generation sequencing has given patients the opportunity to receive targeted therapy if an actionable oncogenic driver is identified.
One such driver is RET fusion, in which the tyrosine kinase domain of RET fuses with upstream gene fragments, leading to constitutive activation and oncogenesis. RET fusions can occur in non–small-cell lung and thyroid cancers as well as GI malignancies.
Subgroup analysis of a phase 1/2 trial demonstrated durable efficacy of selpercatinib (NCT03157128), a highly selective ret proto-oncogene (RET) kinase inhibitor, in patients with locally advanced or metastatic RET fusion-positive GI tumors. Objective response rates were 53.8% and 30.8% in 13 study patients each (n=26) with pancreatic cancer and CRC, respectively. Median durations of response were 52.1 and 13.3 months for pancreatic cancer and CRC, respectively. Based on its efficacy across multiple histologies, selpercatinib received tissue-agnostic approval for treatment of adults with locally advanced or metastatic RET fusion-positive solid tumors.
In a phase 1/2 trial of pralsetinib (NCT03037385), a highly selective RET kinase inhibitor, all 4 patients with RET fusion-positive pancreatic cancer responded to treatment. Currently, pralsetinib is only approved for non–small-cell lung and thyroid cancers with RET alterations.
Do you order next-generation sequencing for patients with locally advanced or metastatic GI tumors? If a RET fusion is identified, would you consider a highly selective RET kinase inhibitor?
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Ali Mirmiran1yrI order it in all metastatic patients. I prefer RET testing as part of NGS.
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KUMAR ABHISHEK1yrYes, all my patients with advanced cancer have NGS done by both tissue and blood based testing at the time of diagnosis. In absence of other standard treatment options, I Show More
