Milind M. Javle, MD

This issue of CCA News highlights the Cholangiocarcinoma Foundation (CCF) 10th Annual Conference held in April. This meeting was chaired by Dr Chiara Branconi, a Lord Kelvin Adam Smith Reader at the University of Glasgow and a medical oncologist with Beatson Cancer Centre; and Dr Laura Goff, medical director of the Vanderbilt-Ingram Cancer Center’s Hematology and Oncology Division.

Dr Javle provides his perspective on important abstracts presented at the ASCO Gastrointestinal Cancers Symposium, held January 19-21, 2023, in San Francisco, CA.

We have recently concluded the 4th Annual CCA Summit, which was held on October 13-15, 2022, in Denver, Colorado.

On September 2, 2022, the US Food and Drug Administration approved durvalumab in combination with gemcitabine/cisplatin for advanced biliary tract cancers (BTCs) on the basis of the TOPAZ-1 study.

A letter from the Editor-in-Chief, Milind M. Javle, MD.

The 2022 ASCO GI Cancers Symposium clearly highlighted the rapid trajectory of clinical research in biliary tract cancers. One of the most eagerly anticipated studies, TOPAZ-1, was presented by Do-Youn Oh, MD, PhD, from Seoul National University Hospital in South Korea. This phase 3 clinical trial enrolled 685 patients and investigated the addition of the PD-L1–directed agent durvalu­mab to gemcitabine and cisplatin chemotherapy backbone versus these chemotherapies alone. The results demonstrated a statistically significant improvement in overall survival (OS), overall response rate (ORR), and progression-free survival (PFS), without dose-limiting toxicities.

Dr Milind Javle provides his perspectives on key presentations on cholangiocarcinoma and biliary tract cancer at the 2022 ASCO Gastrointestinal Cancers Symposium.

The Third CCA Summit was held on October 21-22, 2021 in New Orleans. For the majority of the cholangiocarcinoma (CCA) community, this was their first “live” meeting since the pandemic.

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.

This issue of CCA News features yet another exciting FDA approval for cholangiocarcinoma (CCA), ivosidenib, which was recently approved for CCA with IDH1 mutation. This is the third drug approved for CCA in the past 2 years, highlighting the critical role of molecular profiling in this cancer. Up to 20% of patients with intrahepatic CCA have IDH1 mutation, and the ClarIDHy phase 3 study demonstrated improvement in progression-free survival with ivosidenib versus placebo for chemorefractory disease. The FDA also approved the Oncomine Dx Target Test for IDH1 mutations.

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

On January 15, 2021, experts in the management of patients with cholangiocarcinoma (CCA) convened for a virtual accredited continuing education satellite symposium held during the 2021 annual meeting of the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. The goal was to educate healthcare providers on various aspects of CCA, including epidemiology, current standards of care, unmet clinical needs, the safety and efficacy of fibroblast growth factor receptor (FGFR) inhibitors as second-line therapy, and practical approaches to incorporating FGFR inhibitors into the treatment paradigm for the disease.

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.

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.

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

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.

In this last issue for the year, we are highlighting the proceedings of the Second Annual Cholangiocarcinoma (CCA) Summit, which was conducted on October 22-23, 2020. This summit attracted a wide, multidisciplinary audience and was very interactive, despite being a virtual event. An important focus for this meeting was the emergence of molecular targets in CCA and early successes seen with precision medicine in this disease. Many of the key presentations from the summit are included in the current issue and are highlighted below.

The first confirmed case in the United States of the 2019 novel coronavirus (COVID-19) was reported on January 21, 2020, and as of November 27, 2020, there were >63 million confirmed cases and >1.5 million deaths globally. Despite the global impact, certain populations have been identified as having a higher risk of developing severe COVID-19 infection, including patients with cancer. Various studies have shown that patients with cancer experience particularly poor outcomes after COVID-19 infection. As a result of the pandemic, care delivery has been disrupted to some degree based on the need for prioritization and limitations on resources. Therefore, healthcare providers and patients have been continually reassessing the balance between the benefits and risks of anticancer interventions in the context of the added risk of COVID-19 infection.

While the COVID-19 pandemic rages throughout the world, patients, providers, and healthcare advocates are learning to survive in an alternative (virtual) world that is likely to change the face of medicine forever. Cholangiocarcinoma (CCA) is a complex disease that requires multidisciplinary care. Virtual clinic visits and online tumor boards and symposia represent just a few of the countless innovations introduced over the past year.

It is my great pleasure to launch the inaugural issue of CCA News, an important new publication highlighting the latest research and development in cholangiocarcinoma (CCA). I am proud that we now have a focused publication on biliary tract cancers and am humbled to serve as the first editor-in-chief.

Several hot topics were presented at the recent ASCO 2020 annual meeting about cholangiocarcinoma (CCA), which I would briefly discuss here. First, it was very exciting to see 3 important studies regarding immunotherapy for CCA, which may represent a step forward in the development of CCA therapies.

Treatment options for cholangiocarcinoma continue to evolve. Milind Javle, MD, from MD Anderson Cancer Center, discusses some interesting abstracts from the ASCO 2020 meeting.

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 Vaibhav Sahai discusses different approaches to molecular biomarker testing, including when to order the tests in the course of the disease, use of institutional and commercial testing facilities, and what platforms exist for testing.

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