An umbrella concept for patients with advanced intrahepatic cholangiocarcinoma

While the genomic diversity of biliary tract cancers and the relevance of its primary location have been recognized well, treatment of patients with advanced disease is mostly limited to conventional chemotherapy. However, recent clinical trials (NCT02989857) have shown success of a personalized treatment approach in advanced cholangiocarcinoma patients. Here, we present the umbrella concept of the Liver Cancer Center Heidelberg (LCCH) aiming at personalization of treatment, application of precision medicine, and enrichment of clinical studies.

Patients with advanced intrahepatic cholangiocarcinoma were screened for druggable targets in the LCCH since 2018. The Oncomine™ Comprehensive Assay v3 was used to interrogate genetic alterations in 161 genes. In addition, gene fusions were detected using the Archer Archer® Comprehensive Solid Tumor Assay.

Overall, 51 patients with intrahepatic cholangiocarcinoma were analyzed so far. 75% of detected potentially protumorigenic alterations were considered druggable. Based on the precision oncology concept of the HiGHmed consortium (use case oncology) and adopting the local study portfolio, likely druggable genetic alterations were identified in 77% of patients (range: 1 – 5 drug targets). Druggable gene fusions were observed in 10% of patients. A detailed overview and individual cases will be presented during the meeting.

Our umbrella concept identifies therapeutic targets in most patients suffering from advanced intrahepatic cholangiocarcinoma and thus warrants for a consistent application. The translation of this concept is hampered by the availability of safe drugs to be tested in suitable clinical trials, but may be supported by structural programs for personalized medicine currently developing in Germany (e.g., Zentren für personalisierte Therapie).