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Avapritinib

Avapritinib is for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation.

Ayvakit tradename.

GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST.

Response rate with almost 85% of patients experiencing tumor shrinkage with this targeted drug.

300 mg or 400 mg once daily was provided until disease progression or unacceptable toxicity occurred.

Patients harboring a PDGFRA exon 18 mutation had an overall response rate of 84%, including 7% having complete responses and 77% having partial responses.

Among patients with PDGFRA D842V mutations, the ORR was 89%, with 8% and 82% having complete and partial responses, respectively.

61% of patients had responses that lasted ≥6 months.

The most common side effects reported with avapritinib were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness.

Avapritinib is approved to treat advanced systemic mastocytosis, according to phase 1 and phase 2 clinical trial data.

 

 

Single-agent avapritinib was approved by the FDA for the treatment of adult patients with advanced systemic mastocytosis, including aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

 

 

Ayvakit is the tradename.

 

 

Phase 1 EXPLORER and the phase 2 PATHFINDER trials showed remarkable clinical efficacy to patients with advanced systemic mastocytosis.

 

 

Then daily dose of 200 mg, the overall response rate was 57% which included a complete remission rate of 28% and partial remission rate of 28%. 

 

 

The median response duration was 38.3 months , and there was also a 2.1-month median time to response.

 

 

Adverse effects associated with avapritinib include:  edema, diarrhea, nausea, and fatigue/asthenia. 

 

 

Administration is not recommended in patients with advanced systemic mastocytosis whose platelet count is lower than 50 × 109/L.

 

 

Avapritinib is a kinase inhibitor that is already approved for the treatment of unresectable or metastatic gastrointestinal stromal tumors harboring PDGFRA exon 18 mutations.

 

 

It is a new standard of care for patients with advanced systemic mastocytosis. 

 

 

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