The path to personalized treatment in advanced and metastatic biliary tract cancers: a review of new targeted therapies and immunotherapy

摘要

To summarize targeted therapies and immunotherapy as treatment for advanced/metastatic biliary tract cancers and discuss ongoing clinical trials. For the first time since gemcitabine–cisplatin was set as the standard of care in first-line advanced/metastatic biliary tract cancers in the ABC-02 trial, the combination of durvalumab and gemcitabine–cisplatin has demonstrated a statistically significant improvement of median overall survival in the TOPAZ-1 phase 3 trial. The ABC-06 trial showed a significant increase of median overall survival for FOLFOX and active symptom control compared with active symptom control alone in second-line regardless of molecular and genetic alterations. However, faced with a heterogeneous cancer, patient prognosis remains poor, leaving room for new, personalized, treatment options such as targeted therapies. Efficacy of fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors has been demonstrated in different phase 2 trials for previously treated intrahepatic cholangiocarcinomas harboring FGFR2 fusions. Ivosidenib increases significantly median progression-free survival in previously treated cholangiocarcinomas with isocitrate dehydrogenase-1 (IDH-1) mutation. Other targeted therapies are tested for tumors with HER2 amplifications/mutations, BRAFV600E mutations or KRASG12C mutations. In this review, we aim to follow the changes in the treatment of these tumors, moving from very few chemotherapy options to immunotherapy and targeted therapies in the context of molecular selection of biliary tract cancers subtypes.