Regorafenib, an investigational agent for the treatment of cholangiocarcinoma

ABSTRACT

Introduction

Cholangiocarcinoma is a prevalent gastrointestinal cancer with a high mortality rate. A limited number of cholangiocarcinoma patients are diagnosed with early-stage disease but unfortunately, most patients present with an advanced-stage disease which is not amenable to curative surgical resection.

Areas Covered

We discuss regorafenib, a multi-kinase inhibitor, which has been investigated as a therapeutic agent in advanced stage biliary tract cancer patients in phase II trials. We examined the efficacy and toxicity of this agent and its potential in this patient population in the future. We also provide further insights on novel approaches to optimize the efficacy of regorafenib in cholangiocarcinoma patients.

Expert Opinion

The recent phase II trials of single-agent regorafenib in advanced stage biliary tumors revealed a modest activity in non enriched patient population and is currently part of the national comprehensive cancer network (NCCN) guidelines (Level 2B) in the refractory setting. However, more opportunities for this agent exist in combination approaches with other therapeutics such as immune checkpoint inhibitors. It is also important to recognize that the paradigm has significantly shifted for targeted therapy to more specific and more potent tyrosine kinase inhibitors targeting specific actionable genes.

KEYWORDS:

• Cholangiocarcinoma
• biliary tumors
• regorafenib
• FGFR2
• actionable genes
• TKIs
• targeted therapy

Article highlights

• Advanced stage cholangiocarcinoma is a deadly disease with limited therapeutic options.

• Three phase II trials investigating the single-agent efficacy of regorafenib in advanced stage chemotherapy-refractory biliary tumors showed modest activity and is currently in national comprehensive cancer network (NCCN) guidelines.

• Given recent progress with the promising efficacy of specific targeted therapeutics, the role of regorafenib is limited in the non-FGFR2 enriched patient population.

• Future studies combining regorafenib with immune checkpoint inhibitors may reveal a better therapeutic efficacy based on their synergistic efficacy noted in other solid tumors.

Declaration of interest

R Kim received honorarium from Lilly, BMS, and Incyte, and research funding from Bayer, BMS, and Eisai outside of the submitted work. Other authors declare no competing interests. The authors have no other 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

This paper was not funded.