Monthly Scientific Update – September 2022 (Precision Therapeutics for Intrahepatic Cholangiocarcinoma)

Kelly Butler, Dr. Reham Abdel-Wahab

The traditional chemotherapies gemcitabine and cisplatin have several side effects and have been used to treat cholangiocarcinoma for decades. However, the field of precision oncology is rapidly advancing and generating new, more targeted treatment options.

Every tumor is unique, and precision oncology examines the specific genetic alterations in a patient’s tumor to recommend a particular targeted therapy. Excitingly, multiple targeted therapies have shown clinical benefits for cholangiocarcinoma and are already FDA-approved. For example, ivosidenib, an IDH1 inhibitor, and pemigatimib and infigratinib, FGFR inhibitors, are approved for cholangiocarcinoma patients with IDH1 mutations FGFR2 fusions, respectively. Most research on these targeted therapies has been in clinical trials, which generally investigate one treatment at a time in pre-screened patients who meet certain eligibility criteria, including the presence of a specific mutation.

Moving outside the clinical trial setting, a recent study in Nature investigated the feasibility and efficacy of precision oncology for cholangiocarcinoma in a more general and clinically diverse treatment setting. The study enrolled 101 patients, including 96 intrahepatic cholangiocarcinoma patients, four combined cholangiocarcinoma and hepatocellular carcinoma patients, and only one patient with hepatocellular carcinoma.

All patients had molecular profiling of tumor tissue, identifying specific genetic alterations in 77% of the participants. In accordance with prior research, gene fusions affecting FGFR2 and NRG1 were common, as were mutations of the genes BAP1, ARID1A, FGFR2, IDH1, CDKN2A, CDKN2B, PIK3CA, TP53, ATM, IDH2, BRAF, SMARCA4, and FGFR3. Some of these genetic alterations are targetable by certain drugs already approved or under evaluation in clinical trials. And 59% of patients in the study had targetable genetic alterations. Thus, they were eligible for such treatments, and 32% of these eligible patients received a molecular-matched therapy. Treatment with targeted therapy was associated with improved clinical outcomes compared to traditional chemotherapy.

This result is auspicious, and the field of precision oncology will continue to advance and offer new treatment options for cholangiocarcinoma patients.

Kelly Butler is an NIH Postbac Research Fellow and the Founding Director of SAFE

Reham Abdel-Wahab is the Cholangiocarcinoma Foundation’s Director of Research and Chief Scientific Officer.