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Ref Type Journal Article
PMID (34994649)
Authors Eder JP, Doroshow DB, Do KT, Keedy VL, Sklar JS, Glazer P, Bindra R, Shapiro GI
Title Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas.
Journal Vol Issue Date Pages Journal Short Title
JCO precision oncology 5 2021 Nov 466-472 JCO Precis Oncol
URL
Abstract Text Tumors with neomorphic mutations in IDH1/2 have defective homologous recombination repair, resulting in sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition. The Olaparib Combination trial is a phase II, open-label study in which patients with solid tumors harboring IDH1/2 mutations were treated with olaparib as monotherapy, with objective response and clinical benefit rates as the primary end points.Ten patients with IDH1/2-mutant tumors by next-generation sequencing were treated with olaparib 300 mg twice daily.Three of five patients with chondrosarcomas had clinical benefit, including one patient with a partial response and two with stable disease lasting > 7 months. A patient with pulmonary epithelioid hemangioendothelioma had stable disease lasting 11 months. In contrast, clinical benefit was not observed among four patients with cholangiocarcinoma.These results indicate preliminary activity of PARP inhibition in patients with IDH1/2-mutant chondrosarcoma and pulmonary epithelioid hemangioendothelioma. Further studies of PARP inhibitors alone and in combination in this patient population are warranted.

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