Pharmacotherapeutic options for biliary tract cancer: current standard of care and new perspectives

ABSTRACT

Introduction: Biliary tract cancer (BTC), which comprises gallbladder cancer, ampullary cancer, and cholangiocarcinoma, is a rare and heterogeneous entity, with limited approved therapeutic options. However, interest in this disease has grown exponentially in recent years, as a mounting body of evidence has shed light on the complex molecular and microenvironmental background of BTC, and clinical investigations have explored a variety of new agents and combinations, with promising results.

Areas covered: This review describes the standard of care in advanced BTC and summarizes the most recent evidence available on the pharmacological treatment of resected and advanced disease, focusing on chemotherapy, targeted therapy, and immunotherapy.

Expert opinion: The therapeutic armamentarium of BTC has made radical progress after almost a decade of very few positive results. Phase-III evidence now supports the use of adjuvant capecitabine after resection of localized disease, while investigations into improved regimens in the advanced setting are underway, exploring alternative options to the standard gemcitabine-cisplatin doublet. The first positive phase-III trial supports the use of the mFOLFOX6 regimen as a second-line chemotherapy. Targeted therapy against specific genomic alterations can combine with chemotherapy in specific subsets of patients. Despite recent advancements, conducting clinical trials for BTC is still a real challenge.

KEYWORDS:

• Biliary tract cancer
• chemotherapy
• cholangiocarcinoma
• gallbladder cancer
• gemcitabine
• immunotherapy
• targeted therapy

Article highlights

• After the failure of gemcitabine-based regimens, capecitabine is the first chemotherapeutic option for resected BTC with solid backing evidence.

• A number of studies have explored the benefits of gemcitabine-cisplatin in advanced BTC with respect to specific patient subpopulations.

• Innovative first-line regimens are either based on incorporating a third agent to the gemcitabine-cisplatin doublet, or alternative agents with enhanced antitumor activities or better tolerability.

• Treatment of progressing patients is still an unmet clinical need, but recent phase-III evidence supports the use of mFOLFOX6 regimen as second-line chemotherapy.

• Immunotherapy and targeted therapy are gaining investigational interest in BTC, the latter particularly for the cases presenting with actionable genomic alterations (including FGFR2, IDH1, EGFR, HER2, BRAF, NTRK, and ROS1).

This box summarizes the key points contained in the article.

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 on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Funding was provided by the project Progetto di Rete-NET2011-02352137 “Genomic base triage for target therapy in colorectal cancer - Ricerca Sanitaria Finalizzata 2011” from the Italian Ministry of Health. The authors are also supported by the Fondazione Piemontese per la Ricerca sul Cancro and the Fondazione del Piemonte per l’Oncologia.