Cutaneous toxicity of FDA-approved small-molecule kinase inhibitors

ABSTRACT

Introduction

By 1 January 2021, the FDA has approved a total of 62 small-molecule kinase inhibitors (SMKIs). The increasing clinical use of small-molecule kinase inhibitors has led to some side effects, the most common of which is cutaneous toxicity, as reflected by approximately 90% (57 of 62) of the FDA-approved SMKIs have reported treatment-related cutaneous toxicities. Since these cutaneous toxicities may have a crucial influence on the emotional, physical and psychosocial health of the patients, it is of great importance for doctors, patients, oncologists and interrelated researchers to be aware of the cutaneous side effects of these drugs in order to make the diagnosis accurate and the treatment appropriate.

Areas covered

This review aims to summarize the potential cutaneous toxicities and the frequency of occurrence of FDA-approved 62 SMKIs, and provide a succinct overview of the potential mechanisms of certain cutaneous toxicities. The literature review was performed based on PubMed database and FDA official website.

Expert opinion

It is significant to determine the risk factors for SMKI-induced cutaneous toxicity. The mechanisms underlying SMKI-induced cutaneous toxicities remain unclear at present. Future research should focus on the mechanisms of SMKI-induced cutaneous toxicities to find out mechanistically driven therapies.

KEYWORDS:

• Cutaneous toxicity
• small-molecule kinase inhibitors
• clinical symptom
• incidence
• mechanism

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

A reviewer on this manuscript has disclosed that they are on the advisory board and act as a consultant for Bristol-Myers Squibb, Incyte, Novartis and Pfizer.

Article highlights

• The FDA has approved a total of 62 small-molecule kinase inhibitors as of 1 January 2021.

• Cutaneous toxicity is one of the most common drug adverse events during SMKIs clinical use.

• The potential cutaneous toxicities and the frequency of occurrence of FDA-approved 62 SMKIs were summarized in this review.

• It is significant to determine the risk factors for SMKI-induced cutaneous toxicity.

• The mechanisms and predictive models for cutaneous toxicity attributable to small-molecule kinase inhibitors have not been established.

This box summarizes key points contained in the article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No.81872941) and Science Technology Plan Project of Zhejiang Province (No.2019C04010).