brigatinib

Brigatinib is an oral, small‑molecule tyrosine kinase inhibitor that targets the anaplastic lymphoma kinase (ALK). It is a second‑generation ALK inhibitor designed to overcome certain crizotinib‑resistant mutations and to provide activity in the central nervous system, addressing brain metastases in ALK‑positive non‑small cell lung cancer (NSCLC).

Brigatinib is approved for adults with ALK‑positive NSCLC. It is indicated for patients whose disease has progressed on or who are intolerant to crizotinib, and, in some regions, has been approved as a first‑line therapy based on trials showing improved progression‑free survival and intracranial responses. The agent has demonstrated activity against a range of ALK resistance mutations and tends to have meaningful central nervous system activity.

The mechanism of brigatinib involves inhibition of ALK phosphorylation and downstream signaling, which reduces tumor cell growth. In addition to ALK, brigatinib exhibits activity against several kinases at higher concentrations, contributing to its broader anti‑tumor profile. The drug is administered orally and has a noted ability to penetrate the CNS, contributing to activity against brain metastases.

Dosing typically starts with 90 mg once daily for 7 days, followed by 180 mg once daily. A 7‑day lead‑in reduces the risk of early pulmonary adverse events observed after initiating therapy. Dose adjustments may be needed for hepatic impairment or drug interactions, and patients require monitoring for respiratory symptoms early in treatment.

Common adverse events include nausea, diarrhea, fatigue, cough, dyspnea, and hypertension. Serious risks include interstitial lung disease/pneumonitis, hyperglycemia, liver enzyme elevations, and QT prolongation. In some patients, early pulmonary events may occur within the first week of treatment. Brigatinib is marketed as Alunbrig and was first approved by the FDA in 2017 for post‑crizotinib use, with first‑line approval following in 2020.