Pimitespib therapy for a patient with PDGFRA D842V-mutant gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) with platelet-derived growth factor receptor alpha (PDGFRA) mutations are resistant to tyrosine kinase inhibitors. Pimitespib, a novel heat shock protein 90 inhibitor, was recently approved as a fourth-line treatment for advanced GISTs; however, data on its efficacy against PDGFRA-mutant GISTs remain scarce. We report a case of a 67-year-old male with a gastric GIST harboring a PDGFRA exon 18 Asp842Val mutation. The patient presented with a large peritoneal metastasis at the hepatic hilum and underwent proton beam therapy, achieving 8 months of disease control. However, the tumor progressed thereafter. Regorafenib was introduced but failed immediately owing to tumor penetration. The treatment was switched to pimitespib (160 mg daily, 5 days on, 2 days off, per 21-day cycle), and the patient completed four cycles of the therapy. Post-treatment F-fluorodeoxyglucose (FDG)-positron emission tomography showed a significant reduction in FDG uptake by the metastatic lesion. Pimitespib therapy was eventually discontinued because of duodenal bleeding, with a time to treatment failure of 13 weeks. Although based on a single case, this report demonstrates a significant metabolic response to pimitespib in PDGFRA-mutant GIST. More cases are required to fully elucidate the efficacy of this therapy against such rare tumors.