FDA Approves TKI Inhibitor Brigatinib for ALK-Positive Metastatic NSCLC
Posted: Wednesday, May 27, 2020
On May 22, the U.S. Food and Drug Administration (FDA) approved brigatinib (Alunbrig) as a first-line treatment for adults with ALK-positive metastatic non–small cell lung cancer (NSCLC). An FDA-approved test is required for treatment eligibility. Brigatinib is a next-generation tyrosine kinase inhibitor (TKI) designed to target ALK molecular alterations.
The FDA approval was based on the global, open-label, multicenter phase III ALTA 1L trial. The study enrolled 275 patients with ALK-positive locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. In addition, patients who had brain metastases were included in the clinical trial. Patients were randomly assigned to receive 18 mg of brigatinib once per day orally with a 7-day lead-in at 90 mg once daily (n = 137) or 250 mg of crizotinib twice daily (n = 138).
Patients in the brigatinib arm had a decreased risk of disease progression or death by twofold compared with the crizotinib arm (hazard ratio = 0.49). The median progression-free survival was longer with brigatinib than with crizotinib (24 vs. 11 months). In addition, patients administered brigatinib had a higher confirmed overall response rate of 74%, versus 62% in those given crizotinib. The confirmed intracranial overall response rate in patients with brain metastasis who received brigatinib was 78%, versus 26% in patients given crizotinib.
About 33% of patients administered brigatinib in the trial experienced serious adverse reactions including pneumonia, interstitial lung disease/pneumonitis, pyrexia, dyspnea, pulmonary embolism, and asthenia. Fatal adverse reactions such as pneumonia, cerebrovascular accident, and multiple organ dysfunction syndrome occurred in 2.9% of patients. The most common adverse reactions occurring in more than 25% of patients given brigatinib were diarrhea (49%), fatigue (39%), nausea (39%), rash (38%), cough (37%), myalgia (34%), headache (31%), hypertension (31%), vomiting (27%), and dyspnea (26%).
