FDA Approves Avapritinib as First Targeted Therapy for Rare GIST Mutation

On January 9, 2020, the FDA approved avapritinib (Ayvakit; Blueprint Medicines) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation. This approval was granted Breakthrough Therapy, Fast Track, and Orphan Drug designations by the FDA, and includes GIST that harbors a PDGFRA D842V mutation.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST. However, today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation. Clinical trials showed a high response rate with almost 85% of patients experiencing tumor shrinkage with this targeted drug,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence, in a press statement.

This approval was based on data from a clinical trial of 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with a PDGFRA D842V mutation. Patients in the study were given avapritinib 300 mg or 400 mg once daily until disease progression or unacceptable toxicity occurred. The main outcome measure was overall response rate (ORR).

Patients harboring a PDGFRA exon 18 mutation had an ORR 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.

Although the median response duration was not reached, 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.—Hina Porcelli

Source: US Food and Drug Administration. FDA approves the first targeted therapy to treat a rare mutation in patients with gastrointestinal stromal tumors. January 9, 2020. www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-rare-mutation-patients-gastrointestinal-stromal-tumors. Accessed January 9, 2020.