Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized,...

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Gastrointestinal stromal tumors (GISTs) often develop resistance to tyrosine kinase inhibitors due to mutations in KIT or PDGFRA.
• Avapritinib is a potent inhibitor of KIT- and PDGFRA-mutant kinases, showing promise in earlier studies.

Purpose of the Study:

• To evaluate the efficacy and safety of avapritinib compared to regorafenib in patients with unresectable or metastatic GIST.
• To assess avapritinib as a third-line or later treatment option for advanced GIST.

Main Methods:

• The VOYAGER study was a phase III trial randomly assigning 476 patients 1:1 to avapritinib or regorafenib.
• The primary endpoint was progression-free survival (PFS), with secondary endpoints including objective response rate and overall survival.
• Patients received avapritinib 300 mg daily or regorafenib 160 mg daily with a 1-week off period.

Main Results:

• Median PFS was not statistically different between avapritinib (4.2 months) and regorafenib (5.6 months), with a hazard ratio of 1.25 (P = .055).
• Objective response rates were 17.1% for avapritinib and 7.2% for regorafenib.
• Treatment-related adverse events were similar between the two groups, with high rates for both avapritinib (92.5%) and regorafenib (96.2%).

Conclusions:

• The primary endpoint of the VOYAGER study was not met, as there was no significant difference in median PFS.
• Avapritinib did not demonstrate superior efficacy compared to regorafenib in molecularly unselected, late-line GIST patients.
• Both treatments showed comparable safety profiles in this patient population.