59HYPERION CCA: Gemcitabine/cisplatin/durvalumab with or without adaptive liver-directed radiotherapy for cholangiocarcinoma
Eugene J Koay, Ethan B Ludmir, Sunyoung Lee, Madhu Eluri, Camila Braganca Xavier, Z Ian Hu, Melinda Bachini, Juan W Valle, Milind JavleAbstract
Background and Objectives
Patients with advanced stages of intrahepatic cholangiocarcinoma (iCCA) often die of liver failure due to the tumor growing and blocking the blood vessels and/or bile ducts of the liver. The standard of care treatment for patients with advanced iCCA is chemoimmunotherapy and results in a median overall survival (OS) of 12.8 months. We have shown in retrospective studies that radiotherapy directed at the primary cancer results in high rates of liver tumor control for patients with advanced iCCA, translating to a median OS after radiotherapy of 21 months. Here, we will test the hypothesis that liver-directed radiotherapy after at least 4 months of chemoimmunotherapy will improve OS compared to chemoimmunotherapy alone. We also will measure progression free survival and patient-reported quality of life as secondary endpoints.
Methods
Patients can be pre-enrolled before completing at least 4 months of chemoimmunotherapy. After receiving this required amount of chemoimmunotherapy and having scans that show no progression of disease, patients can enroll and will be randomized in a 2:1 manner to (arm 1) liver-directed radiotherapy followed by maintenance immunotherapy or (arm 2) completion of chemoimmunotherapy for at least 6 months followed by maintenance immunotherapy. The study will randomize 126 patients into these two arms and compare their outcomes in terms of the primary and secondary endpoints. Exploratory endpoints will involve correlations with imaging, blood- and tissue-based biomarkers.
Results
The study activated in August 2025 at MD Anderson Cancer Center. Updated accrual and follow up will be reported at the conference. 8 other sites are expected to open the study across North America. Sister studies are also planned at international sites.
Conclusion
Successful completion of this study with support of the hypothesis that liver-directed radiotherapy improves OS would potentially change how we take care of patients with advanced iCCA.