A 45-year-old woman has a gastric mass biopsy showing spindle cells with perinuclear vacuolization, positive for CD117 and DOG1, negative for CD34. Mutation analysis reveals a PDGFRA exon 18 D842V substitution. Which therapeutic agent is most likely to be ineffective for this tumor?
- A Avapritinib
- B Sunitinib
- C Imatinib ✓
- D Ripretinib
Correct answer: C. Imatinib
Explanation
PDGFRA D842V mutation in GIST is characteristically resistant to imatinib, which cannot effectively bind the altered ATP-binding pocket. This mutation accounts for approximately 6% of all GISTs and almost all are imatinib-resistant. Avapritinib (BLU-285) was specifically designed to overcome D842V resistance and has received FDA approval for this mutation. Sunitinib and ripretinib have activity in imatinib-resistant disease but less specifically for D842V.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.