Abrupt onset of severe parkinsonism in a patient with metastatic gastrointestinal stromal tumor receiving treatment with avapritinib: A case report()

Gastrointestinal stromal tumors (GISTs) are tumors of the digestive tract. To date, there have been no neurological paraneoplastic syndromes or symptoms associated with metastatic GISTs. Tyrosine kinase inhibitors (TKIs) are the typical class of agents used in management of this malignancy. Avapritinib, a new TKI, has been associated with myriad neurological adverse events with fairly rapid resolution in clinical trials. Herein, we present the case of a patient with metastatic GIST who, after starting treatment with avapritinib, developed rapidly progressive and persisting severe neuropsychiatric symptoms, including profound parkinsonism and encephalopathy, while concurrently receiving therapy with the antipsychotic olanzapine. We posit that the patient could be conceptualized as having a relative vulnerability to medication effects in the setting of metastatic GIST - possibly driven by an immune-mediated process - and that the addition of avapritinib triggered an overtly evident, clinically significant cascade of neurological deterioration.