Targeted Treatment for Gastrointestinal Stromal Tumor Mutation Gains FDA Approval

Avapritinib represents the first ever treatment for a rare mutation for patients with gastrointestinal stromal tumors.

The US Food and Drug Administration (FDA) has approved avapritinib (Ayvakit), the first ever targeted treatment for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) with a rare mutation.

The new treatment, developed by Blueprint Medicines Corporation, targets tumors that harbor the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation, the most common exon 18 mutation.

The new treatment is a kinase inhibitor that blocks the kinase enzyme, while helping keep cancer cells from growing.

"GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST,” Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, said in a statement. “However, today's approval provides patients with the first drug specifically approved for GIST harboring this mutation.”

In a 43-patient clinical trial, 85% of patients experienced tumor shrinkage using the targeted medication. In the study, patients received either 300 mg or 400 mg of treatment orally daily until disease progression or they experienced unacceptable toxicity.

Investigators determined that 300 mg once daily was the recommended dose.

For the subgroup of patients with PDGFRA D842V mutations, the overall response rate was 89%, with 8% having a complete response and 82% having a partial response.

Common side effects included edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness.

Avapritinib may also cause intracranial hemorrhage, central nervous system effects, including cognitive impairment, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations, and can cause harm to a developing fetus or newborn baby.

GISTs arise from specialized nerve cells in the walls of the gastrointestinal tract that aid in the movement of food through the intestines and control various digestive processes.

The activating mutations in PDGFRA have been linked to the development of GISTs, with up to approximately 10% of GIST cases involve mutations of this gene.