Initial US Approval

  • 20171

Indications

Metastatic ALK+ NSCLC:

  • The treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test1

Recommended Dose/Route

  • Brigatinib 90 mg orally once daily for the first 7 days; then increase the dose to 180 mg orally once daily.1
Brigatinib: Dose Reduction

Brigatinib: Dose Reduction

Pivotal Study

ALTA 1L (NCT02737501)2

  • Treatment setting: TKI-naive advanced ALK+ NSCLC
  • Key Inclusion Criteria: Eligible participants in ALTA 1L included patients with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. 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.
  • Treatment: Brigatinib 180 mg orally once daily with a 7-day lead-in at 90 mg once daily.

ALTA (NCT02094573)3

  • Treatment setting: locally advanced or metastatic ALK+ NSCLC following progression on crizotinib.
  • Key Inclusion Criteria: Participants in ALTA included patients with advanced or metastatic ALK-positive NSCLC who had experienced disease progression while receiving treatment with crizotinib and an ECOG Performance Status of 0-2.
  • Treatment: Brigatinib 90 mg once daily (90 mg arm; n = 112) or 180 mg once daily following a 7-day lead-in at 90 mg once daily (90→180 mg arm; n = 110).
Brigatinib: Efficacy Data

Brigatinib: Efficacy Data


Safety

ALTA 1L (Treatment Naive)

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were diarrhea (53%), rash (40%), cough (35%), fatigue (32%), hypertension (32%), nausea (30%), myalgia (28%), dyspnea (25%), abdominal pain (24%), headache (22%), vomiting (21%), back pain (21%), and pruritus (20%).1
  • Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were increased creatine phosphokinase (81%), increase AST (72%), increased lipase (59%), hyperglycemia (56%), increased ALT (52%), increased amylase (52%), decreased lymphocytes (41%), decreased phosphorous (41%), hemoglobin decreased (41%), increased alkaline phosphatase (36%), increase creatinine (25%), increased potassium (24%), increased calcium (22%), and decreased magnesium (21%).1
  • Dosage Reduction Due to AEs: 38%1
  • Permanent Discontinuation Due to AEs: 13%1

ALTA (Previously Treated)

  • Common Adverse Reactions (≥20%): The most frequently reported any grade adverse events (AEs) were nausea (33%), fatigue (29%), headache (28%), dyspnea (27%), vomiting (24%), and decreased appetite (22%).1
  • Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were increased AST (38%), hyperglycemia (38%), increased ALT (34%), increased creatinine phosphokinase (27%), increased amylase (27%), anemia (23%), prolonged activated partial thromboplastin time (22%), and increased lipase (21%).
  • 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)
Brigatinib: Most Common Adverse Events of Grade 3 or 4

Brigatinib: Most Common Adverse Events of Grade 3 or 4

References

  1. Alunbrig (brigatinib). Prescribing information. Takeda Pharmaceuticals America, Inc; 2024. Accessed December 12, 2024. https://www.alunbrig.com/sites/default/files/2022-10/prescribing-information.pdf
  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
  4. Dziadziuszko R, Peters S, Ruf T, et al. Clinical experience and management of adverse events in patients with advanced ALK-positive non-small-cell lung cancer receiving alectinib. ESMO Open. 2022;7(6):100612. doi:10.1016/j.esmoop.2022.100612
  5. Zhou F, Yang Y, Zhang L, et al. Expert consensus of management of adverse drug reactions with anaplastic lymphoma kinase tyrosine kinase inhibitors. ESMO Open. 2023;8(3):101560. doi:10.1016/j.esmoop.2023.101560
  6. Camidge DR, Pabani A, Miller RM, Rizvi NA, Bazhenova L. Management Strategies for Early-Onset Pulmonary Events Associated with Brigatinib. Journal of Thoracic Oncology. 2019;14(9):1547-1555. doi:10.1016/j.jtho.2019.04.028
  7. National Institute of Diabetes and Digestive and Kidney Diseases. Brigatinib (LiverTox). In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Accessed November 26, 2024. http://www.ncbi.nlm.nih.gov/books/NBK548523/