Current and emerging therapies for advanced biliary tract cancers
| Autor: | Rachna T. Shroff, Audrey E. Kam, Ashiq Masood |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty IDH1 medicine.medical_treatment Antineoplastic Agents Targeted therapy Cholangiocarcinoma Internal medicine Biomarkers Tumor Humans Immunologic Factors Medicine Molecular Targeted Therapy Neoplasm Staging Trametinib Chemotherapy Hepatology business.industry Gallbladder Palliative Care Gastroenterology Microsatellite instability Dabrafenib Immunotherapy medicine.disease Biliary Tract Neoplasms medicine.anatomical_structure business medicine.drug |
| Zdroj: | The Lancet Gastroenterology & Hepatology. 6:956-969 |
| ISSN: | 2468-1253 |
| DOI: | 10.1016/s2468-1253(21)00171-0 |
| Popis: | Biliary tract cancers (cholangiocarcinomas and gallbladder cancers) are increasing in incidence and have a poor prognosis. Most patients present with advanced disease, for which the treatment is palliative chemotherapy. Over the past few years, the genomic landscape of biliary tract cancers has been examined and several targeted therapies have been developed. Molecular targets with clinically meaningful activity include fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), RAS-RAF-MEK (MAP2K1)-ERK (MAPK3), HER2 (also known as ERBB2), DNA mismatch repair, and NTRK. Pemigatinib, a FGFR1-3 inhibitor, showed encouraging response rates and survival data as second-line treatment and received US Food and Drug Administration (FDA) approval in April, 2020, for previously treated advanced or metastatic cholangiocarcinoma with FGFR2 gene fusion or rearrangements. Ivosidenib, an IDH1 inhibitor, showed improved progression-free survival versus placebo in second-line treatment in the phase 3 ClarIDHy trial. Early phase trials of dabrafenib plus trametinib (BRAF and MEK inhibition) and zanidatamab (a bispecific HER2-antibody) have yielded encouraging response rates. Immunotherapy has mainly produced responses in tumours with deficient mismatch repair or high microsatellite instability (also known as dMMR or MSI-H) or higher PD-L1 score, or both. However, early phase trials of immunotherapy plus chemotherapy in unselected patient populations appear promising. NTRK inhibitors have also shown promise in early phase trials of NTRK-fusion positive solid tumours, including cholangiocarcinoma. In this Review, we discuss current and emerging therapies for advanced biliary tract cancers, with a focus on molecularly targeted therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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