Abstract
Simple SummaryThe incidence of cholangiocarcinomas is rising. The prognosis of this heterogeneous group of tumors remains poor. Standard chemotherapy options are limited and frequently not effective. Recently, extensive molecular profiling identified key actionable drivers leading to successful biomarker-selected clinical trials. A number of novel targeted therapy drugs and immune checkpoint inhibitors are under investigation. In this review we summarized recent progress in the systemic treatment of cholangiocarcinomas, highlighting biomarkers and therapies in ongoing early-phase clinical trials.Cholangiocarcinomas (CCAs) comprise of a heterogeneous group of cancers arising in the biliary tract (intrahepatic or iCCA, perihilar or pCCA and distal or dCCA; the latter are known under the collective term of eCCA), each subtype having its own particularities in carcinogenesis, management and prognosis. The increasing incidence in recent decades, limited treatment options and high mortality rates, even in the early stages, have led to an imperious need for more in-depth understanding and development of tailored treatments for this type of aggressive tumour. The wide use of molecular profiling has increased the understanding of biology and identified key molecular drivers, for example, IDH1 mutations or FGFR2 fusions for iCCA, or BRAF mutations in eCCA. Most recently, the FDA approved pemigatinib, an FGFR inhibitor and ivosidenib, an IDH1 inhibitor, but even though progress has been made to better understand the mechanisms of tumorigenesis, genetic make-up, and tumour resistance to standard chemotherapy and targeted therapies, cholangiocarcinomas still represent an important challenge in the daily clinical practice of oncology. The purpose of this review is to highlight the recent progress in the systemic treatment of advanced/metastatic CCAs with a focus on targeted drugs and their biomarkers currently evaluated in early-phase clinical trials.
Highlights
Cholangiocarcinomas comprise of a heterogeneous group of malignancies arising from the epithelium of the biliary tract, of which approximately 90% are adenocarcinoma
In patients with cholelitiasis, PD-1/PD-L1 levels were downregulated. These findings suggest that the PD-1/PD-L1 pathway may play an important role in carcinogenesis and the progression of hepatitis B virus (HBV)-positive iCCAs [38]
Significant progress has been made in understanding the biology of CCAs, subsequently leading to improved outcomes for a subgroup of patients with known genetic alterations
Summary
Cholangiocarcinomas comprise of a heterogeneous group of malignancies arising from the epithelium of the biliary tract, of which approximately 90% are adenocarcinoma. A recent randomised phase-2 study showed that regorafenib compared to the best supportive care improved progression-free survival in patients who received a prior gemcitabine/cisplatin based therapy—the benefit was marginal, with no impact on overall survival [4]. With such modest treatment results [5], and a survival rate of less than 10% at 5 years [6], the need to understand tumour biology and the underlying disease mechanisms is a priority. Recent progress in the systemic treatment of advanced/metastatic cholangiocarcinomas (CCAs) is discussed with a focus on targeted drugs and their biomarkers currently evaluated in early-phase clinical trials
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
