Metabolism, toxicity and management of fruquintinib: a novel drug for metastatic colorectal cancer

ABSTRACT

Introduction

Colorectal cancer (CRC) is the third most diagnosed cancer globally and despite therapeutic strides, the prognosis for patients with metastatic disease (mCRC) remains poor. Fruquintinib is an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) targeting VEGFR −1, −2, and −3, and has recently received approval by the U.S. Food and Drug Administration for treatment of mCRC refractory to standard chemotherapy, anti-VEGF therapy, and anti-epidermal growth factor receptor (EGFR) therapy.

Areas covered

This article provides an overview of the pre-clinical data, pharmacokinetics, clinical efficacy, and safety profile of fruquintinib, as well as the management of clinical toxicities associated with fruquintinib.

Expert opinion

Fruquintinib is a valuable additional treatment option for patients with refractory mCRC. The pivotal role of vigilant toxicity management cannot be understated. While fruquintinib offers a convenient and overall, well-tolerated treatment option, ongoing research is essential to determine its efficacy in different patient subsets, evaluate it in combination with chemotherapy and immunotherapy, and determine its role in earlier lines of therapy.

KEYWORDS:

• Colon cancer
• fruquintinib
• metastatic cancer
• rectal cancer
• targeted therapy
• vascular endothelial growth factor

Article highlights

• Fruquintinib is a potent and selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) −1, −2, and −3.

• The phase 3 FRESCO trial demonstrated survival benefit in Chinese patients with metastatic colorectal cancer (mCRC) who had received at least two prior lines of systemic therapy (not including regorafenib or tipiracil-trifluridine) when compared to placebo.

• The phase 3 FRESCO-2 trial demonstrated survival benefit in an international cohort of patients with mCRC who had progressed on first- and second-line therapy, including regorafenib or tipiracil-trifluridine (most patients had received prior VEGF inhibition), when compared to placebo.

• Fruquintinib demonstrates a favorable toxicity profile, with unique adverse effects including hypertension, hand-foot syndrome, and proteinuria, which may be mitigated with close monitoring and intervention.

• Future studies should aim to assess the role of fruquintinib in combination with standard chemotherapy, in combination with immunotherapy, and in earlier lines of therapy.

Disclosure of interest

A Mahipal: Astrazeneca (Speakers Bureau, Advisory board), Exelexis (Speakers Bureau), Taiho Oncology (Advisory Board), Pfizer (Research Funding), Elevar Therapeutics (Advisory Board). 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.

Author contributions

All authors contributed to the manuscript, and all approved the final article.

Additional information

Funding

This paper was not funded.