Researchers from Israel reported the cases of 2 patients with advanced medullary thyroid carcinoma (MTC) who developed an acute confusional state following pralsetinib treatment. “To our knowledge, this is the first report of such an association,” the researchers wrote in Acta Oncologica

Pralsetinib is an oral tyrosine kinase selective RET inhibitor. RET is the most commonly implicated gene in MTC. Pralsetinib, sold under the brand name Gavreto®, was approved by the US Food and Drug Administration (FDA) in 2020 to treat patients aged 12 or more years with advanced or metastatic RET-mutant MTC.

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The patients described in this study developed an acute confusional state 1 and 6 weeks after the initiation of pralsetinib treatment, respectively, and improved shortly after the cessation of treatment, with no other interventions necessary. They both received the treatment at the recommended dose of 400 mg once a day. 

“These cases encourage a high degree of caution and increased awareness of possible neurological deterioration when administering pralsetinib among caretakers, and a thorough neurological assessment should be undertaken,” the researchers wrote.

They propose that treatment should be started at a low dose and the dosage should be incrementally increased according to the tolerance of the patient to reach optimum dosage and prevent serious adverse events or irreversible damage.

Acute confusional state, also known as delirium, is a clinical state that is characterized by disturbed consciousness, cognitive function, or perception. It usually develops over a short period and is the result of a medical condition, substance intoxication, or side effect of medication.

As more patients will be treated with pralsetinib following its approval by the FDA, more similar cases may be seen, better clarifying the mechanism and clinical significance of this adverse event, the study authors wrote.

Reference

Shachar E, Peleg Hasson S, Blumenthal D, et al. Practical lessons from treating medullary thyroid carcinoma patients harboring a RET-alteration: pralsetinib-induced acute confusional state. Acta Oncol. Published online May 9, 2022. doi:10.1080/0284186X.2022.2071111