Olaparib in treatment‐refractory isocitrate dehydrogenase 1 (<i>IDH1</i>)– and <i>IDH2</i>‐mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial
Olaparib does not have sufficient single-agent activity to warrant further development in IDH-mutant CCA. However, a subgroup of patients demonstrated CB, and exploratory analysis revealed this subgroup to be enriched for lower baseline 2-HG levels. Future clinical trials leveraging the HRD properties of IDH mutations are warranted with enhanced patient selection and novel combination therapies.
Authors
- Deborah B. Doroshow (ORCID: https://orcid.org/0000-0002-2221-9818)
- Azeet Narayan (ORCID: https://orcid.org/0000-0003-1820-7934)
- Nataliya V. Uboha (ORCID: https://orcid.org/0000-0003-3449-1680)
- Mary Jo Pilat (ORCID: https://orcid.org/0000-0002-8854-1543)
- Gabriel Tinoco (ORCID: https://orcid.org/0000-0002-2565-6124)
- Monica Niger (ORCID: https://orcid.org/0000-0002-9055-5338)
- Simon Khagi (ORCID: https://orcid.org/0000-0002-6434-9135)
- Jordi Rodón (ORCID: https://orcid.org/0000-0001-6467-3632)
- Xun Bao (ORCID: https://orcid.org/0000-0003-4895-8536)
- Ranjit S. Bindra (ORCID: https://orcid.org/0000-0002-3255-0467)
- Dennis Vu (ORCID: https://orcid.org/0000-0002-2623-963X)
- Roman Groisberg (ORCID: https://orcid.org/0000-0001-8970-7675)
- Geoffrey Ira Shapiro (ORCID: https://orcid.org/0000-0002-3331-4095)
- Michael Cecchini (ORCID: https://orcid.org/0000-0003-3504-0128)
- Derek Shyr (ORCID: https://orcid.org/0000-0002-2345-3390)
- Nilofer S. Azad (ORCID: https://orcid.org/0000-0002-9613-3988)
- Yu Shyr (ORCID: https://orcid.org/0000-0003-2086-9670)
- Patricia LoRusso (ORCID: https://orcid.org/0000-0001-7144-036X)
- Abhijit A. Patel (ORCID: https://orcid.org/0000-0003-3943-5610)
- Diane E. Durecki (ORCID: https://orcid.org/0000-0002-6486-556X)
- Elizabeth J. Davis (ORCID: https://orcid.org/0000-0001-7626-2435)
- Biswajit Das (ORCID: https://orcid.org/0000-0002-1929-3646)
- May Cho (ORCID: https://orcid.org/0000-0002-7152-0017)
- S. Percy Ivy (ORCID: https://orcid.org/0000-0001-7747-072X)
- Scott A. Boerner (ORCID: https://orcid.org/0000-0003-1388-9665)
- Kristen Spencer (ORCID: https://orcid.org/0000-0001-5577-3439)
- Jan Drappatz (ORCID: https://orcid.org/0000-0001-8187-7119)
- Benjamin Powers (ORCID: https://orcid.org/0000-0002-9406-8916)
- Jing Li (ORCID: https://orcid.org/0000-0001-8669-4901)
- Li Chen (ORCID: https://orcid.org/0000-0002-3965-8833)
Institutions
- Rutgers, The State University of New Jersey (US)
- Hoag Memorial Hospital Presbyterian (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Wisconsin–Madison (US)
- Harvard University (US)
- Johns Hopkins University (US)
- University of Pittsburgh (US)
- Wayne State University (US)
- Vanderbilt University (US)
- University of California, Irvine (US)
- Johns Hopkins Medicine (US)
- Yale University (US)
- The Barbara Ann Karmanos Cancer Institute (US)
- The University of Kansas Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- Frederick National Laboratory for Cancer Research (US)
- National Cancer Institute (US)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Vanderbilt-Ingram Cancer Center
- Rutgers Cancer Institute (US)
- The Ohio State University (US)
- New York University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Cancer
- Published
- 2025-02-07
- DOI
- https://doi.org/10.1002/cncr.35755
- Citations
- 8
- Primary Topic
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Type
- article
- Field-Weighted Citation Impact
- 16.05
Funders
- Ben and Catherine Ivy Foundation
- Rising Tide Foundation
- National Cancer Institute