Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas. (2021)

• Record Type: Journal Article
• Authors: Eder, Joseph P.; Doroshow, Deborah B.; Do, Khanh T.; Keedy, Vicki L.; Sklar, Jeffrey S.; Glazer, Peter; Bindra, Ranjit; Shapiro, Geoffrey I.
• Is Part Of: JCO precision oncology. Volume 5(2021)
• Publication Date: 2021
• Subjects: Precision Medicine; Neoplasms; Pharmacogenetics; Molecular Targeted Therapy; Personalized medicine; Oncology; Pharmacogenomics; Periodical; Periodicals; 616.994
• DOI: 10.1200/PO.20.00247
• Languages: English
• ISSNs: 2473-4284

Abstract

Abstract : PURPOSE: 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. METHODS: Ten patients with IDH1/2-mutant tumors by next-generation sequencing were treated with olaparib 300 mg twice daily. RESULTS: 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. CONCLUSION: 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.