Biliary tract cancers(BTC)are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens.For more than a decade,the combination of gemcitabine and cis-platin has served a...Biliary tract cancers(BTC)are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens.For more than a decade,the combination of gemcitabine and cis-platin has served as the first-line standard treatment.There are few choices for second-line chemo-therapy.Targeted treatment with fibroblast growth factor receptor 2 inhibitors,neurotrophic tyrosine receptor kinase inhibitors,and isocitrate dehydrogenase 1 inhibitors has had important results.Immune checkpoint inhibitors(ICI)such as pembrolizumab are only used in first-line treatment for microsatellite instability high patients.The TOPAZ-1 trial's outcome is encouraging,and there are several trials underway that might soon put targeted treatment and ICI combos into first-line options.Newer targets and agents for existing goals are being studied,which may represent a paradigm shift in BTC management.Due to a scarcity of targetable mutations and the higher toxicity profile of the current medications,the new category of drugs may occupy a significant role in BTC therapies.展开更多
Patients with unresectable cholangiocarcinoma(CCA)face a poor prognosis,and there are few effective treatment options for the disease.The standard of care for patients with locally advanced or metastatic CCA is chemot...Patients with unresectable cholangiocarcinoma(CCA)face a poor prognosis,and there are few effective treatment options for the disease.The standard of care for patients with locally advanced or metastatic CCA is chemotherapy with a gemcitabine-based doublet.Unfortunately,the clinical benefit obtained with these regimens is modest,with a median overall survival of about one year.For CCA that is chemotherapy-refractory or recurs after first-line chemotherapy,the treatment options are even more limited,and no relevant randomized controlled data are available.In recent years,molecular profiling has shed light on the molecular basis of CCA and identified subgroups of patients that might benefit from a personalized treatment approach.These efforts resulted in the recent FDA approval of the fibroblast growth factor receptor(FGFR)inhibitor,pemigatinib,as a second-line treatment for patients with advanced CCA harboring an FGFR2-fusion or rearrangement.Several other targeted agents also are under evaluation in patients with CCA,of which the isocitrate dehydrogenase inhibitor has had the most promising results.Finally,immunotherapy is being explored as a new treatment approach for advanced CCA patients;indeed,the immune checkpoint inhibitor pembrolizumab can already be used to treat CCAs that are mismatch repair deficient.This review is a comprehensive overview of the treatment options for CCA and offers a glimpse into what the future could hold for these patients.展开更多
文摘Biliary tract cancers(BTC)are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens.For more than a decade,the combination of gemcitabine and cis-platin has served as the first-line standard treatment.There are few choices for second-line chemo-therapy.Targeted treatment with fibroblast growth factor receptor 2 inhibitors,neurotrophic tyrosine receptor kinase inhibitors,and isocitrate dehydrogenase 1 inhibitors has had important results.Immune checkpoint inhibitors(ICI)such as pembrolizumab are only used in first-line treatment for microsatellite instability high patients.The TOPAZ-1 trial's outcome is encouraging,and there are several trials underway that might soon put targeted treatment and ICI combos into first-line options.Newer targets and agents for existing goals are being studied,which may represent a paradigm shift in BTC management.Due to a scarcity of targetable mutations and the higher toxicity profile of the current medications,the new category of drugs may occupy a significant role in BTC therapies.
文摘Patients with unresectable cholangiocarcinoma(CCA)face a poor prognosis,and there are few effective treatment options for the disease.The standard of care for patients with locally advanced or metastatic CCA is chemotherapy with a gemcitabine-based doublet.Unfortunately,the clinical benefit obtained with these regimens is modest,with a median overall survival of about one year.For CCA that is chemotherapy-refractory or recurs after first-line chemotherapy,the treatment options are even more limited,and no relevant randomized controlled data are available.In recent years,molecular profiling has shed light on the molecular basis of CCA and identified subgroups of patients that might benefit from a personalized treatment approach.These efforts resulted in the recent FDA approval of the fibroblast growth factor receptor(FGFR)inhibitor,pemigatinib,as a second-line treatment for patients with advanced CCA harboring an FGFR2-fusion or rearrangement.Several other targeted agents also are under evaluation in patients with CCA,of which the isocitrate dehydrogenase inhibitor has had the most promising results.Finally,immunotherapy is being explored as a new treatment approach for advanced CCA patients;indeed,the immune checkpoint inhibitor pembrolizumab can already be used to treat CCAs that are mismatch repair deficient.This review is a comprehensive overview of the treatment options for CCA and offers a glimpse into what the future could hold for these patients.
