Officials with the FDA have approved avapritinib (Ayvakit, Blueprint Medicines) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. This medication is the first precision therapy approved to treat a genomically defined population of patients with GIST, according to Blueprint.

The approval was based on efficacy results from the phase 1 NAVIGATOR clinical trial, as well as combined safety results from multiple clinical trials for avapritinib. In patients with PDGFRA exon 18 mutant GIST, avapritinib had an overall response rate (ORR) of 84% (95% CI: 69%, 93%), and a median duration of response (DOR) was not reached.
The most common adverse reactions (≥20 percent) reported by patients were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness. 

GIST is a rare, genomically driven sarcoma of the gastrointestinal (GI) tract. Approximately 6% of patients with newly diagnosed GIST have PDGFRA exon 18 mutations. The most common PDGFRA exon 18 mutation is the D842V mutation, which is resistant to all other approved therapies. A retrospective study showed that when these patients were treated with imatinib, they had an ORR of 0%.

"For the first time, we can offer these patients a highly effective treatment that targets the underlying genetic cause of their disease," said Michael Heinrich, MD, Professor of Medicine at Oregon Health & Science University and an investigator on the NAVIGATOR trial, in a prepared statement. "Building on our growing understanding of the molecular basis of GIST, this milestone ushers in a new era of precision medicine in this disease. The FDA approval represents a call to action to conduct mutational testing in all patients with GIST before initiating kinase inhibitor therapy, as recommended by clinical guidelines, so appropriate patients may realize the benefits of this promising new medicine."
Blueprint Medicines plans to make its avapritinib product available in the United States within a week.

REFERENCE
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]. Cambridge, MA; January 9, 2020: Blueprint Medicines. http://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-announces-fda-approval-ayvakittm-avapritinib. Accessed January 9, 2020.