Angela Lamarca, MD, PhD, MSc

Angela Lamarca, MD, PhD, MSc, Consultant (FEA) in Medical Oncology presents an overview of key abstracts on cholangiocarcinoma (CCA) presented at the 2022 annual meeting of the ESMO World Congress on Gastrointestinal Cancer (ESMO GI 2022).

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

Drs Juan Valle and Angela Lamarca discuss clinical studies being conducted to improve the use of chemotherapy in CCA by exploring molecular biomarkers that could help patient selection for optimal response to certain chemotherapy regimens.

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.

Using efficacy and safety data in selecting among FGFR inhibitors in cholangiocarcinoma

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

Dr Angela Lamarca discusses the use of FGFR inhibitors in daily practice. Their use will depend largely on data from currently ongoing second- and first-line clinical trials. She suggests that consideration should be given to their use in combination with chemotherapy and/or as maintenance therapy after first-line chemotherapy. Dr Milind Javle summarizes the field, suggesting that a time may come when patients with CCA are never treated with chemotherapy at all. Pemigatinib was FDA approved as second-line therapy in cholangiocarcinoma in May 2020.

Dr Vaibhav Sahai reviews the toxicities that have been encountered in clinical trials with FGFR inhibitors. He suggests that most of these adverse events are class effects and include hyperphosphatemia (which is relatively easy to manage with dietary restrictions and phosphate-binding agents), nail and hair changes, stomatitis, and retinal epithelial changes. In contrast, Dr Angela LaMarca considers the adverse events associated with chemotherapy, including myelosuppression, nausea, vomiting, diarrhea, and others. Dr Milind Javle suggests that the toxicities encountered with chemotherapy are significantly worse than those with FGFR inhibitors.

Dr Angela Lamarca reviews the current clinical trials with FGFR inhibitors, particularly those with patients with FGFR2 fusion and other genetic aberrations. Dr Vaibhav Sahai highlights those FGFR inhibitors that are nonselective and those that are selective for FGFR1-4, and discusses the clinical trial results with the selective inhibitors, including pemigatinib and infigratinib. He remarks that the response rates and progression-free survival in these trials have been remarkable, far better than what is seen with chemotherapy.

Dr Vaibhav Sahai and Dr Angela Lamarca consider options for managing patients with CCA while awaiting results from biomarker testing, which can take 3 to 6 weeks. They discuss starting these patients on first-line chemotherapy and then switching appropriate patients to second-line targeted therapy, and also speak to the increased utility of next-generation sequencing in CCA.

Dr Angela Lamarca discusses approaches to first- and second-line therapy for patients with advanced CCA.