Brigatinib: Indications, Dosing, Mechanism of Action and Side Effects

Indications

Brigatinib is a new generation anaplastic lymphoma kinase (ALK) inhibitor. It has been approved for the treatment of adult anaplastic lymphoma kinase (ALK)-positive patients with metastatic non-small cell lung cancer (NSCLC), and is recommended by the National Comprehensive Cancer Network (NCCN) as a preferred first-line, Class 1 treatment option for ALK+ advanced or metastatic NSCLC.

In the latest results from its Phase III clinical trial, the ALK inhibitor brigatinib was shown to be superior to crizotinib in patients with untreated non-small cell lung cancer. Brigatinib showed longer progression-free survival, higher objective response rates, better efficacy against brain metastases, and less impairment of patients' quality of life.

Dosing

The recommended dosage for Brigatinib (ALUNBRIG) is:

90 mg orally once daily for the first 7 days; then increase the dose to 180 mg orally once daily.

Administer ALUNBRIG until disease progression or unacceptable toxicity.

If ALUNBRIG is interrupted for 14 days or longer for reasons other than adverse reactions, resume treatment at 90 mg once daily for 7 days before increasing to the previously tolerated dose.

ALUNBRIG may be taken with or without food. Instruct patients to swallow tablets whole. Do not crush or chew tablets.

No dose adjustment is required in patients with mild or moderate hepatic impairment. The dose of brigatinib should be reduced by approximately 40 per cent in patients with severe hepatic impairment.

Mechanism of Action

Brigatinib is a tyrosine kinase inhibitor with activity against a variety of kinases, including ALK, ROS1, insulin-like growth factor 1 receptor, and epidermal growth factor receptor deletion and point mutations. Patients with ALK-positive NSCLC produce an aberrant form of ALK in their bodies, which stimulates the division and growth of cancer cells with uncontrolled use. Brigatinib acts by inhibiting ALK phosphorylation and activation of downstream signalling proteins, leading to a reduction in cancer growth and spread.

Side Effects

Adverse effects of Brigatinib are tolerated and controlled. The most common adverse reactions include: diarrhoea, malaise, nausea, rash, cough, myalgia, headache, hypertension, vomiting and dyspnoea. Other possibly more serious adverse reactions include: pneumonitis, hyperglycaemia, hypertension, bradycardia, visual disturbances, hepatotoxicity, photosensitivity and abnormal biochemical markers (e.g., elevated creatine phosphokinase (CPK) and pancreatic enzymes, lymphopenia).

References:

[1] Brigatinib Outperforms Crizotinib as First-Line Therapy.[J]. Cancer discovery, 2020. DOI:10.1158/2159-8290.CD-NB2019-143.

[2] NEERAJ GUPTA. Clinical Pharmacology of Brigatinib: A Next-Generation Anaplastic Lymphoma Kinase Inhibitor.[J]. Clinical Pharmacokinetics, 2023. DOI:10.1007/s40262-023-01284-w.

[3] MICHAEL J HANLEY. Brigatinib pharmacokinetics in patients with chronic hepatic impairment.[J]. Investigational New Drugs, 2023. DOI:10.1007/s10637-023-01339-6.