Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: evidence to date and future perspectives

ABSTRACT

Introduction

Biliary tract cancers (BTCs) are poor prognosis malignancies usually classified in intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. In the last few years, novel treatment targets have been identified in iCCA patients, including fibroblast growth factor receptor (FGFR) aberrations; thus, several FGFR inhibitors are currently being developed, some of which have already suggested interesting efficacy and adequate safety in phase I and phase II trials regarding refractory iCCA.

Areas covered

This review provides an overview regarding the current scenario of FGFR2 targeted therapies in iCCA, especially focusing on the mechanism of action and clinical development of futibatinib (TAS-120), a highly selective irreversible pan-FGFR antagonist. According to the interim analysis of the FOENIX-CCA2 trial, whose results have been presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, futibatinib could lead to meaningful benefit in patients affected by previously treated iCCA with FGFR2 gene fusions or other rearrangements.

Expert opinion

Because of its promising and durable activity, futibatinib has the potential to become a novel therapeutic option in the treatment of iCCAs harboring FGFR2 aberrations. Further studies are warranted to confirm the efficacy of this investigational molecule.

KEYWORDS:

• Intrahepatic cholangiocarcinoma
• biliary tract cancer
• futibatinib
• tas-120
• fgfr2
• FGFR
• targeted therapies
• foenix-CCA2
• Cholangiocarcinoma
• liver cancer

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.

Article highlights

• Biliary tract cancers (BTCs) are poor prognosis malignancies usually classified in intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer.

• In the last few years, genomic studies have begun to unveil the molecular landscape of BTC, uncovering several potentially actionable aberrations; thus, comprehensive genomic profiling is playing an increasing role in BTC, especially in iCCA

• The role of FGFR-targeted therapies has been recently evaluated in several clinical trials and various agents have been tested or are currently under investigation in iCCA

• Among these agents, futibatinib (TAS-120) recently attracted a lot of attention, with results of an interim analysis of the phase II FOENIX-CCA2 trial which have been presented at the ASCO 2020 Virtual Meeting

• Because of its promising and durable activity, futibatinib has the potential to represent a novel therapeutic option in the treatment of iCCAs harboring FGFR2 aberrations

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.