Tucatinib: an investigational novel therapeutic agent for the treatment of HER-2 colorectal cancer

ABSTRACT

Introduction

Human epidermal growth factor receptor 2 (HER-2) is an oncogenic driver and target in gastroesophageal and breast cancer; there is also evidence for a role in non-small cell lung cancer (NSCLC). In colorectal cancer (CRC), the incidence of HER-2 overexpression occurs in up to 10% of patients. While its role of HER-2 as a biomarker for prognosis in CRC remains uncertain, it remains of interest as a potential therapeutic target. Tucatinib is an investigational agent which functions as a selective HER-2 inhibitor.

Areas covered

In this article, the authors discuss the incidence of HER-2 in CRC and its rationale in the treatment of CRC. An overview of the market is offered, followed by a scientific summary of tucatinib including its clinical development in CRC.

Expert opinion

Tucatinib is a selective HER-2 inhibitor that has unique properties which distinguishes it from other HER-2 directed therapies. In the clinical setting, it has demonstrated clinical efficacy of HER-2 inhibition across various solid tumors including CRC. Given the evidence of clinical activity observed with tucatinib in breast cancer and frequency of HER-2 overexpression in CRC, the investigation of tucatinib as a monotherapy and in combination with other therapeutic agents remains of interest.

KEYWORDS:

• Colorectal cancer
• ERBB2
• HER-2
• ONT-380
• tucatinib

Article highlights

• HER-2 (ERBB2) amplifications have been demonstrated in a wide variety of cancers, including colorectal cancer where there is an unmet for effective therapies in refractory setting.

• Tucatinib is highly selective for HER-2 with a tolerable safety profile compared to other HER-2 directed therapies.

• Promising clinical activity from the combination of tucatinib and trastuzumab was observed in the phase II clinical trial in patients with treatment refractory HER-2 amplified colorectal cancer.

• An expansion is ongoing to evaluate the efficacy of tucatinib monotherapy and to validate the reported findings in the MOUNTANEER trial.

• Future considerations include investigating the efficacy of tucatinib in earlier lines of treatment as well in other patient populations including those who weakly express HER-2 amplification (1+ or 2+/ISH negative).

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

This paper was not funded.