FDA Approves Brigatinib for Metastatic ALK-Positive Non–Small Cell Lung Cancer
On April 28, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval to brigatinib (Alunbrig) for the treatment of patients with metastatic anaplastic lymphoma kinase (ALK)-positive non–small cell lung cancer (NSCLC) who have had disease progression on or are intolerant to crizotinib.
ALTA Trial
Approval was based on the noncomparative, two-arm, open-label, multicenter ALTA clinical trial demonstrating a clinically meaningful and durable overall response rate in patients with locally advanced or metastatic ALK-positive NSCLC that had progressed during crizotinib therapy. All patients had tumors with a documented ALK rearrangement based on an FDA-approved test or a different test with adequate archival tissue to confirm ALK arrangement by the Vysis® ALK Break-Apart fluorescence in situ hybridization Probe Kit test. A total of 222 patients were randomized to brigatinib orally at either 90 mg once daily (n = 112) or 180 mg once daily following a 7-day lead-in at 90 mg once daily (n = 110).
Overall response rate was assessed by an independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR was 48% (95% CI: 39%, 58%) in the 90-mg arm and 53% (95% confidence interval [CI] = 43%–62%) in the 180-mg arm. After a median follow-up of 8 months, median duration of response was 13.8 months in both arms. In patients with measurable brain metastases at baseline, the intracranial response rate was 42% (95% CI = 23%–63%) in the 90-mg arm (n = 26) and 67% (95% CI = 41%–87%) in the 180-mg arm (n = 18). Median intracranial duration of response was not estimable in the 90-mg arm and was 5.6 months in the 180-mg arm. Among patients who exhibited an intracranial response, 78% in the 90-mg arm and 68% in the 180-mg arm maintained an intracranial response for at least 4 months.
Adverse Reactions
Safety was evaluated in 219 patients who received at least one dose of brigatinib in the ALTA trial.
The most common adverse reactions, occurring in at least 25% of patients taking brigatinib, were nausea, diarrhea, fatigue, cough, and headache. Visual disturbances also occurred in patients receiving brigatinib. The most common serious adverse reactions were pneumonia and interstitial lung disease/pneumonitis.
Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia in 2 patients and sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urosepsis in 1 patient each. Adverse reactions leading to permanent discontinuation of brigatinib occurred in 2.8% and 8.2% of patients receiving 90 mg and 180 mg, respectively.
Patients receiving brigatinib should be monitored for new or worsening respiratory symptoms; hypertension; bradycardia; visual symptoms; and elevations in amylase, lipase, blood glucose, and creatine phosphokinase.
The recommended dosing regimen of brigatinib is 90 mg orally once daily for the first 7 days and then, if tolerated, an increase to 180 mg orally once daily.
Full prescribing information is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208772lbl.pdf.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
