Initial US Approval
20171
Indications
The treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test. This indication is approved based on objective response rate (ORR) and duration of response (DOR) reported in pivotal studies.1
Recommended Dose/Route
90 mg orally once daily for the first 7 days; then increase the dose to 180 mg orally once daily.1
Brigatinib: Dose Reduction
Pivotal Study
ALTA 1L (NCT02737501)2, ALTA (NCT02094573)3
Key Inclusion Criteria: Eligible participants in ALTA 1L included patients with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy.1 Eligible patients were allowed to have up to 1 prior regimen of chemotherapy in the locally advanced or metastatic setting and were required to have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. Participants in ALTA included patients with advanced or metastatic ALK-positive NSCLC who had experienced disease progression while receiving treatment with crizotinib.1
Treatment
Brigatinib 180 mg orally once daily with a 7-day lead-in at 90 mg once daily.1
Brigatinib: Efficacy Data
Safety (Treatment Naïve, ALTA 1L)
The most frequently reported adverse events (AEs) of any grade in patients receiving brigatinib included diarrhea (53%), rash (40%), cough (35%), fatigue (32%), hypertension (32%), and nausea (30%).1 Serious AEs occurred in 33% of patients receiving brigatinib; the most common were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal adverse reactions occurred in 2.9% of patients and included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).1
Dosage Reduction Due to AEs: 38%1
Permanent Discontinuation Due to AEs: 13%1
Safety (Previously Treated, ALTA)
Serious AEs occurred in 38% of patients in the 90 mg group and 40% of patients in the 90→180 mg group; the most common were pneumonia (5.5% overall) and ILD/pneumonitis (4.6% overall).1 Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urosepsis (1 patient each). The most frequent AEs leading to discontinuation of brigatinib were ILD/pneumonitis (0.9% in the 90 mg group and 1.8% in the 90→180 mg group) and pneumonia (1.8% in the 90→180 mg group only). The most common AE that led to dose reduction was increased creatine phosphokinase for both regimens (1.8% in the 90 mg group and 4.5% in the 90→180 mg group).1
Dosage Reduction Due to AEs1: 7.3% (90 mg group), 20% (90→180 mg group)
Permanent Discontinuation Due to AEs1: 2.8% (90 mg group), 8.2% (90→180 mg group)
References
1. Alunbrig (brigatinib). Package insert. Takeda Pharmaceuticals America, Inc; February 2022.
2. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018;379(21):2027-2039. doi:10.1056/NEJMoa1810171
3. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitor-naive advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021;16(12):2091-2108. doi:10.1016/j.jtho.2021.07.035