First approved by the U.S. Food and Drug Administration in 2020 for treatment of gastrointestinal stromal tumors (GIST), avapritinib’s (AyvakitTM) approval was extended in 2021 for treatment of advanced systemic mastocytosis (AdvSM). Both approvals are for patients with PDGFR-alpha genetic variants.
Targeted therapy, kinase inhibitor
Mechanism of Action
Targets PDGFR-alpha and PDGFR-alpha D842 variants to inhibit autophosphorylation of KIT D816V and D842a, reducing resistance to kinase inhibitors
Treatment of unresectable GIST and AdvSM in adults with PDGFR-alpha exon 18 variant, including PDGFR-alpha D842V
300 mg orally once daily for GIST and 200 mg orally once daily for AdvSM
Administer avapritinib by mouth once daily on an empty stomach, at least one hour before or two hours after a meal.
More than 20% of patients in the drug’s clinical trials experienced edema, nausea, fatigue, asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness. Cognitive impairment can include memory changes, confusion, somnolence, or speech disorders. Serious intracranial hemorrhage was reported in less than 3% of patients.
A missed dose can be taken up to eight hours before the next dose is due. A vomited dose should not be repeated; instead, patients should wait and take the next dose on schedule.
Avoid coadministration with strong and moderate CYP3A inhibitors. If not possible, the dose may need to be reduced. Avoid coadministration with strong and moderate CYP3A inducers.
Test for pregnancy and advise patients to use effective contraception during treatment because of the risk of embryo-fetal toxicity. Monitor platelet counts before and during treatment.
Watch for and report signs of intracranial hemorrhage, such as severe headache, vomiting, drowsiness, dizziness, confusion, slurred speech, or paralysis. Do not operate hazardous machinery if you are experiencing cognitive effects.
Avapritinib can impair fertility; inform your healthcare team immediately of a known or suspected pregnancy. If you are of reproductive potential, use effective contraception while taking avapritinib and for six weeks after the final dose. Do not breastfeed when taking avapritinib and for at least two weeks after the final dose.
No differences in safety or efficacy were noted in patients older than 65 compared to younger patients.
Avapritinib is considered a hazardous drug because of reproductive risk. It can cause embryo-fetal toxicity.