FDA Approves Therascreen PDGFRA To Identify Patients Eligible for Treatment With Avapritinib

FDA Approves Therascreen PDGFRA To Identify Patients Eligible for Treatment With Avapritinib

The FDA has approved the therascreen PDGFRA kit to identify patients with gastrointestinal stromal tumors (GIST) who are eligible for treatment with avapritinib (Ayvakit).¹

Avapritinib is approved as a treatment option for adult patients with unresectable or metastatic GIST whose disease harbors a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including DGFRA D842V mutations. The companion diagnostic is designed to detect the D842V somatic mutation in the PDGFRA gene using genomic DNA that has been extracted from a patient’s formalin-fixed paraffin-embedded tumor tissue.

It is estimated that 6% of patients with newly diagnosed GIST have a PDGFRA exon 18 mutation, and PDGFRA mutations represent the most common variants.

“The therascreen PDGFRA kit is an FDA-approved and validated test, delivering results in a fast turnaround time,” Jonathan Arnold, vice president and head of Translational Science and Precision Diagnostics at Qiagen, said in the press release. “This ensures that physicians receive results promptly, enabling them to make informed treatment decisions for their patients [with GIST] in a timely and effective manner.”

In 2020, avapritinib was approved in the United States. The approval was supported by findings from the phase 1 NAVIGATOR trial (NCT02508532), which demonstrated that among patients with a PDGFRA exon 18—mutation (n = 43), the agent elicited an 84% overall response rate (95% CI, 69%-93%), including a 7% complete response rate and a 77% partial response rate. At a median follow-up time of 10.6 months (range, 0.3-24.9 months), the median duration of response was not reached, and 61% of responding patients with exon 18 mutations had a response that lasted 6 months or longer.²

Avapritinib is an oral tyrosine kinase inhibitor. The recommended dose for avapritinib is 300 mg once daily. Patients should take the medicine on an empty stomach, at least 1 hour before and 2 hours after a meal.³

The most common adverse events associated with treatment are edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness.

The prescribing label for avapritinib comes with warnings for intracranial hemorrhage, central nervous system (CNS) effects and embryo-fetal toxicity. Manifestations of CNS may include cognitive impairment, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations. In the event of grade 1 or 2 intracranial hemorrhage reactions, clinicians should withhold treatment and then allow patient to resume treatment at a reduced dose after the toxicity has resolved. If a grade 3 or 4 reaction—or recurrent grade 1 or 2 reaction—occurs, treatment should be permanently discontinued.

Of note, concurrent treatment with strong and moderate CYP3A inhibitors should be avoided. If this cannot be avoided, the avapritinib dose should be reduced. Concurrent treatment with strong and moderate CYP3A inducers should also be avoided.

References

1. QIAGEN receives FDA approval for companion diagnostic to Blueprint Medicines’ AYVAKIT® (avapritinib) in gastrointestinal stromal tumors. News release. QIAGEN N.V. August 7, 2023. Accessed August 8, 2023. yhoo.it/43V4Hzf
2. Blueprint Medicines announces FDA approval of Ayvakit (avapritinib) for the treatment of adults with unresectable or metastatic PDGFRA exon 18 mutant gastrointestinal stromal tumor. News release. Blueprint Medicines. January 9, 2020. Accessed August 8, 2023. https://bit.ly/2sTz3GX.
3. Ayvakit. Prescribing information. Blueprint Medicines Corporation; 2023. Accessed May 22, 2023. bit.ly/45pbnr9