by Dr. C.H. Weaver M.D. 5/2020
Updated data released from the Phase 3 ALTA-1L clinical trial evaluating Alunbrig (brigatinib) versus Xalkori (crizotinib) in patients with advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor show that with 25 months of follow up Alunbrig continues to demonstrate overall and intracranial effectiveness compared to Xalkori, reinforcing its potential as a first-line therapy for ALK+ NSCLC. (1,8) On May 22, 2020, the US FDA approved Alunbrig for the treatment of ALK-positive metastatic NSCLC based on efficacy outcomes from the ALTA 1L clinical trial.
Alunbrig is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit the ALK fusion protein in NSCLC. In April 2017, Alunbrig received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for treatment of ALK+ metastatic NSCLC patients who have progressed on or are intolerant to Xalkori.
About ALK+ NSCLC
Non-small cell lung cancer is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million individuals diagnosed with lung cancer each year worldwide. (2) Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients (3) and three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene. (4-6)
About the ALTA-1L Trial
The phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) clinical trial of Alunbrig is an ongoing trial which enrolled 275 patients with ALK+ locally advanced or metastatic NSCLC who had not received prior treatment with an ALK inhibitor. Patients received either Alunbrig, 180 mg once daily with seven-day lead-in at 90 mg once daily, or Xalkori, 250 mg twice daily and were directly compared. Twenty-nine percent of patients had brain metastases at baseline in the Aluinbrig arm versus 30% in the Xalkori arm. Twenty-six percent of patients received prior chemotherapy for advanced or metastatic disease in the Alunbrig arm versus 27% in the Xalkori arm.
Overall 74% of Alunbrig treated patients responded to treatment compared to 62% treated with Xalkori translating to an average survival duration without disease progression of 24 months compared with 11 months for those receiving Xalkori. The most common side effects were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension and vomiting.
With more than two years of follow-up the study has demonstrated that Alunbrig reduced the risk of disease progression or death by 76% in newly diagnosed patients whose disease had spread to the brain at time of enrollment and by 57% in all patients.
The response rate for patients with measurable brain metastases was 78% for Alunbrig compared to 26% for Xalkori. Alunbrig demonstrated superior and durable responses in the brain compared to Xalkori.
- Takeda Presents Long-Term Data in ALK+ NSCLC Showing ALUNBRIG® (brigatinib) Continues to Demonstrate Superiority in the First-Line After Two Years of Follow-U
- American Cancer Society. What is Non-Small Cell Lung Cancer?. Accessed May 11, 2019
- Kris MG, et al. JAMA, 2014;311:1998-2006.
- Gainor JF, Varghese AM, Ou SH, et al. Clin Cancer Res. 2013;19(15):4273-81.
- Koivunen JP, Mermel C, Zejnullahu K, et al. Clin Cancer Res. 2008; 14(13):4275-83.
- Wong DW, Leung EL, So KK, et al. Cancer. 2009; 115(8):1723-33.
- Chia PL, Mitchell P, Dobrovic A, John T. Clin Epidemiol, 2014;6:423-432.
- US Food and Drug Administration. FDA approves brigatinib for ALK-positive metastatic NSCLC. May 22, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-brigatinib-alk-positive-metastatic-nsclc. Accessed May 26, 2020.