Current and emerging immunotherapeutic approaches for biliary tract cancers

Area of Science:

• Oncology
• Immunotherapy
• Gastroenterology

Background:

• Biliary tract cancers (BTCs) are aggressive malignancies with poor prognoses.
• Current chemotherapy benefits for advanced BTCs have plateaued, necessitating novel therapeutic strategies.
• While targeted therapies show promise, their application is limited by the low frequency of specific driver alterations in BTCs.

Purpose of the Study:

• To review current and emerging immunotherapeutic approaches for biliary tract cancers (BTCs).
• To evaluate the efficacy and safety of immunotherapies in advanced BTCs.
• To identify potential biomarkers for predicting response to immunotherapy.

Main Methods:

• Literature search of PubMed, Web of Science, and meeting resources (January 2017-May 2022).
• Inclusion of clinical trial information from clinicaltrials.gov and chictr.org.cn.
• Focus on immune checkpoint inhibitors (ICIs) and other immunotherapeutic modalities.

Main Results:

• Immune checkpoint inhibitors (ICIs) are under investigation for BTCs, with benefit primarily seen in microsatellite-instability high (MSI-H)/DNA mismatch repair-deficient (dMMR) or tumor mutational burden-high (TMB-H) subgroups.
• Combinations of ICIs with chemotherapy demonstrate promising efficacy and moderate toxicity in advanced BTCs.
• The durvalumab plus GEMCIS combination significantly improved survival in the TOPAZ-1 trial, suggesting a new frontline therapy option.

Conclusions:

• Immunotherapy, particularly in combination with chemotherapy, shows significant potential for treating advanced BTCs.
• The combination of ICIs with chemotherapy is likely to become a new standard first-line treatment for advanced BTCs.
• Further research is required to optimize immunotherapy combinations and identify reliable predictive biomarkers.