Related Experiment Video
Updated: Oct 7, 2025
Evaluating In Vitro DNA Damage Using Comet Assay
Published on: October 11, 2017
Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas
Joseph P Eder1, Deborah B Doroshow1,2, Khanh T Do3
1Yale Cancer Center, New Haven, CT.
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.
Insights
Poly (ADP-ribose) polymerase (PARP) inhibition shows preliminary activity in IDH1/2-mutant chondrosarcoma and pulmonary epithelioid hemangioendothelioma. Further research is needed for these rare tumor types.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neomorphic mutations in isocitrate dehydrogenase 1/2 (IDH1/2) are found in various solid tumors.
- IDH1/2 mutations lead to defective homologous recombination repair, creating synthetic lethality vulnerabilities.
- This defect confers sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors.
Purpose of the Study:
- To evaluate the efficacy of olaparib monotherapy in patients with solid tumors harboring IDH1/2 mutations.
- To determine objective response and clinical benefit rates as primary endpoints in the Olaparib Combination trial.
Main Methods:
- A phase II, open-label study was conducted.
- Ten patients with IDH1/2-mutant tumors, confirmed by next-generation sequencing, were enrolled.
- Patients received olaparib 300 mg orally twice daily.
Main Results:
- Three of five patients with chondrosarcoma achieved clinical benefit, including one partial response and two with stable disease (>7 months).
- One patient with pulmonary epithelioid hemangioendothelioma had stable disease for 11 months.
- No clinical benefit was observed in four patients with cholangiocarcinoma.
Conclusions:
- Preliminary activity of PARP inhibition was observed in IDH1/2-mutant chondrosarcoma and pulmonary epithelioid hemangioendothelioma.
- These findings suggest potential therapeutic value of PARP inhibitors in specific IDH1/2-mutant tumor types.
- Further investigation of PARP inhibitors, both as monotherapy and in combination, is warranted for this patient population.
