Antoine Hollebecque, MD

Understanding more about the molecular biology of cholangiocarcinoma will improve its treatment

Clinical studies are required to define role of targeted therapy in cholangiocarcinoma

Drs Javle, Bañales, and Hollebecque discuss the innate and acquired resistance pathways to FGFR inhibitors in cholangiocarcinoma and how these pathways can have important effects on clinical outcomes. They also look ahead to ongoing clinical trials evaluating next-generation FGFR inhibitors that may be able to overcome resistance mechanisms and improve progression-free and overall survival in cholangiocarcinoma.

Advantages and disadvantages of liquid biopsy in CCA

Rational choices for combination therapy in CCA

Using next-generation sequencing to detect FGFR fusion partners and co-mutations to improve efficacy in treating CCA

Evaluating the impact of FGFR inhibitors on the quality of life in patients with CCA

Managing hyperphosphatemia and RPED in patients treated with FGFR inhibitors

Drs Javle, Báñales, and Hollebecque describe their thoughts about the use of pan-FGFR inhibitors compared with those that primarily target FGFR2 and the potential of treating CCA with inhibitors of FGFR1, 3, and 4. Moreover, they consider the most common adverse events associated with inhibitors of FGFR2, of which the most difficult to manage are hyperphosphatemia, nail toxicity, eye toxicity, and fatigue. The importance of educating oncologists on how to treat these toxicities is key to maintaining dose intensity of FGFR inhibitors.

Drs Javle and Hollebecque review the phase 2 clinical trial efficacy data of pemigatinib, infigratinib, and futibatinib as second-line therapy of FGFR2 fusion–positive cholangiocarcinoma, and explore use of these agents in the first-line and adjuvant settings.

A discussion of the molecular biology of the FGFR pathway in the growth and development of cholangiocarcinoma.