Brigatinib in the first-line treatment of ALK+ metastatic NSCLC: safety and efficacy

ABSTRACT

Introduction: Among the oncogene-addicted non-small cell lung cancer patients, those bearing ALK rearrangement can be currently treated with next-generation ALK inhibitors. Brigatinib was first used to treat Crizotinib-resistant patients because it can target resistance mutations in ALK fusion protein. Recently, Brigatinib was also studied as upfront treatment of newly diagnosed ALK-positive patients.

Areas covered: We outline the drug profile of Brigatinib as first-line treatment and compare it with other ALK inhibitors available. The context of ALK-rearranged non-small cell lung cancer and pharmacological aspects of Brigatinib are reviewed before the analysis of the results from the study ALTA-1 L in terms of efficacy and safety.

Expert opinion: The superior efficacy of Brigatinib over Crizotinib as first-line treatment is undoubted. Consequently, Brigatinib is a new option in untreated ALK+ metastatic NSCLC patients, among the other drugs available for this indication, such as Ceritinib and Alectinib. Each of these ALK inhibitors has a specific tolerability profile, so that the choice may be also guided by patient preference according to potential side effects. In the future other factors could impact treatment choice, for instance the kind of resistance ALK mutations develop under treatment could influence the sequence of ALK inhibitors.

KEYWORDS:

• Non-small cell lung cancer
• oncogene-addicted
• ALK inhibitor
• brigatinib
• ALTA-1L

Article highlights

• Among the oncogene-addicted non-small cell lung cancer patients, those with ALK translocation have the option of many specific targeted drugs.

• Brigatinib is one of the available ALK inhibitors, which was initially studied to overcome resistance to Crizotinib.

• Recently, the results of the phase III ALTA-1L trial, comparing up-front Brigatinib versus Crizotinib, were published.

• The superiority of Brigatinib over Crizotinib is similar to that observed for other second-generation ALK inhibitors, such as Alectinib.

• Third-generation ALK inhibitors like Lorlatinib and Ensartinib are also showing superiority over Crizotinib.

Reviewer disclosures

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

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.

Additional information

Funding

This paper received no funding.