Lorlatinib for the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer

ABSTRACT

Introduction

Approximately 3–5% of patients with non-small cell lung cancer （NSCLC）belonged to anaplastic lymphoma kinase (ALK)-positive NSCLC. The treatment drugs of ALK-positive NSCLC mainly included crizotinib, ceritinib, alectinib, and brigatinib. Although these drugs had some effects, most of them were usually easy to develop drug resistance. Lorlatinib is a new inhibitor of ALK for treating ALK-positive NSCLC,the effect is obvious, and not easy to develop resistance.

Areas covered

The main mechanism of action, pharmacokinetics, clinical efficacy and safety of lorlatinib were introduced in this paper.

Expert commentary

Lorlatinib is a new, reversible, ATP-competitive small molecule inhibitor of ALK and c-ros oncogene 1 (ROS1). It can inhibit tumor cell growth in ALK- and ROS1-overexpressing tumor cells. Clinical trial indicated that lorlatinib had obvious therapeutic effect for patients with ALK-positive NSCLC. Lorlatinib could also pass through the blood-brain barrier, which had a good effect on patients with brain metastasis. Adverse events of lorlatinib were mostly mild and moderate in severity, and patients were easily tolerated. Most common adverse events were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.

KEYWORDS:

• Anaplastic lymphoma kinase
• c-ros oncogene 1
• lorlatinib
• non-small cell lung cancer
• brain metastasis

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 manuscript was not funded.