March 2021, Vol 2, No 1

Dear Colleagues, It gives me great pleasure to introduce the March issue of CCA News. Once again, we have several recent developments in cholangiocarcinoma (CCA) clinical research, and these have been reviewed by leaders in the field.

I first learned of cholangiocarcinoma (CCA) in 2015, when my husband Steve was diagnosed with stage IV inoperable intrahepatic CCA and was given a prognosis of less than a year to live. He defied the prognosis and survived for 40 months, until his death in March 2019. When he was diagnosed, neither one of us had ever heard the word “cholangiocarcinoma” and did not know it was possible to have cancer in the bile duct. We both knew that a diagnosis of other gastrointestinal (GI) cancers, such as pancreatic or colon cancer, could be catastrophic and were stunned to realize that the treatment options and outcomes for patients with CCA were the most dismal of all GI cancers.

Final results from the phase 3 clinical trial ClarIDHy showed that ivosidenib (Tibsovo), a first-in-class oral inhibitor of isocitrate dehydrogenase 1 (IDH1) mutation, prolonged the median overall survival (OS) in patients with previously treated advanced cholangiocarcinoma (CCA) and IDH1 mutation. Although this improvement did not reach statistical significance, after adjusting for crossovers from the placebo to the ivosidenib group, the difference in median OS was statistically significant.

In February 2021, Basilea Pharmaceuticals reported early results from the phase 2 FIDES-01 clinical trial (NCT03230318), which is evaluating the efficacy of derazantinib, an investigational small-molecule FGFR1-3 inhibitor, in patients with inoperable or advanced intrahepatic cholangiocarcinoma (CCA) and FGFR2 gene fusions or FGFR2 gene mutations or amplifications. Derazantinib also inhibits the colony-stimulating factor 1 receptor kinase (CSF1R). CSF1R-mediated signaling is important for the maintenance of tumor-promoting macrophages.

The rationale for immunotherapy in biliary tract cancers is strong, because these cancers are inflammatory in nature, according to Abby Siegel, MD, MS, Executive Director and PDT Lead, Hepatobiliary Oncology, Global Clinical Development at Merck. Inroads are being made into biomarkers predictive of response to immunotherapy in biliary cancers, Dr Siegel said at the 2020 Annual Cholangiocarcinoma Summit.

A periadjuvant, or perioperative, approach to the treatment of biliary tract cancers, including cholangiocarcinoma (CCA), has several potential advantages that may offer an opportunity to improve outcomes in these diseases, said James Harding, MD, Regional Director, Early Drug Development, Memorial Sloan Kettering Cancer Center, New York, NY, at the 2020 Annual Cholangiocarcinoma Summit.

Flavio Rocha, MD, Hepatopancreatobiliary Surgeon, Virginia Mason Medical Center, Director of Research, Digestive Disease Institute, and Associate Medical Director of the Floyd and Delores Jones Cancer Institute, Seattle, WA, provided an overview of the changes made in the 8th edition of the AJCC’s tumor, node, metastasis (TNM) staging system at the 2020 Annual Cholangiocarcinoma Summit. These changes have direct implications for the management of patients with hilar or intrahepatic CCA.