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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 JCO precision oncology
Vol 5
Issue
Date 2021 Nov
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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
IDH2 V305M missense unknown IDH2 V305M does not lie within any known functional domains of the Idh2 protein (UniProt.org). V305M has been identified in the scientific literature (PMID: 34994649), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Jan 2022).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH1 R132S chondrosarcoma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in stable disease lasting 10 months in a patient with chondrosarcoma harboring IDH1 R132S (PMID: 34994649, NCT02576444). 34994649
IDH2 V305M malignant epithelioid hemangioendothelioma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in stable disease lasting 11 months in a patient with pulmonary epithelioid hemangioendothelioma harboring IDH2 V305M (PMID: 34994649, NCT02576444). 34994649
IDH1 R132C chondrosarcoma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in a partial response with 59% tumor reduction lasting 14 months in one patient and stable disease lasting 7.5 months in one patient out of four patients with chondrosarcoma harboring IDH1 R132C (PMID: 34994649, NCT02576444). 34994649