학술논문

Clinical Efficacy of Olaparib in IDH1/IDH2- Mutant Mesenchymal Sarcomas.
Document Type
Article
Source
JCO Precision Oncology. 9/1/2021, Vol. 5, p466-472. 7p.
Subject
*OLAPARIB
*POLY ADP ribose
*GAIN-of-function mutations
*SARCOMA
*NUCLEOTIDE sequencing
*POLY(ADP-ribose) polymerase
Language
ISSN
2473-4284
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. [ABSTRACT FROM AUTHOR]