Advances in pharmacotherapy for cholangiocarcinoma: from conventional therapies to targeted drugs

ABSTRACT

Introduction

Cholangiocarcinomas (CCA) are rare, highly invasive tumors often diagnosed at an advanced disease stage with an associated poor prognosis. Surgery represents the only chance for curative-intent treatment, but recurrence rates remain high. Neoadjuvant or adjuvant chemotherapy are options for patients with resectable CCA to increase recurrence-free survival and overall survival, while palliative chemotherapy represents the treatment for unresectable disease. Global efforts are currently focused on the development of novel more effective therapies.

Areas covered

A review was conducted in August 2021 using the PubMed database with the following keywords: ‘cholangiocarcinoma,’ ‘chemotherapy,’ and ‘therapy.’ Manuscripts reporting on first- and second-line chemotherapy, neoadjuvant and adjuvant treatment regimens, and targeted therapies currently being tested or employed in the management of CCA were examined.

Expert opinion

The prognosis of CCA is negatively affected by several factors including a lack of reliable biomarkers leading to delayed diagnoses, high inter- and intra-tumoral heterogeneity, and few effective chemotherapy regimens. In pursuit of more effective therapies, ongoing trials are testing both conventional and targeted drugs.

KEYWORDS:

• Chemotherapy
• cholangiocarcinoma
• targeted therapies

Highlight box

- Cholangiocarcinomas are highly invasive tumors with poor prognosis

- CisGem is the preferred regimen for primary treatment of unresectable and metastatic biliary tract cancer according to the most recent guidelines

- FOLFOX is recommended by guidelines as the preferred regimen for subsequent-line therapy of biliary tract cancer with disease progression

- Trials on IDH and FGFR inhibitors have now reached the phase III stage of clinical investigation with promising results in terms of OS and PFS among patients with advanced and refractory biliary tract cancers. Trials testing the efficacy and safety of PD-1 and PDL-1 inhibitors are also ongoing.

- Despite the lack of solid evidence, current guidelines recommend adjuvant chemotherapy with capecitabine for 6 months after surgery.

- While the benefit of neoadjuvant therapy in CCA remains unproven, and therefore not included in current international guidelines, the use of preoperative systemic therapy has intuitive appeal given the generally poor biology and early recurrence among patients undergoing surgical resection

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.