On March 24, 2022, Brigatinib (also known as brigatinib) was approved by the State Food and Drug Administration for use in ALK-positive locally advanced or metastatic disease First-line therapy in patients with non-small cell lung cancer (NSCLC).
Previously, on April 28, 2017, the U.S. Food and Drug Administration (FDA) approved the marketing of brigatinib for ALK-positive patients with disease progression who were intolerant to crizotinib or had disease progression after treatment. of patients with metastatic non-small cell lung cancer.
On May 22, 2020, the U.S. Food and Drug Administration approved brigatinib as a first-line treatment for adult patients with ALK-positive metastatic non-small cell lung cancer.
Brigatinib is a novel dual inhibitor of ALK and EGFR, its unique dimethyl phosphine oxide (DMPO) structure enhances the binding to ALK protein , enhances the activity of the drug, and also creates favorable conditions for the drug to pass through the blood-brain barrier and maintain the blood concentration of the drug in the brain, and can widely inhibit a variety of ALK fusion types and drug resistance mutations.
Trade Name: Alunbrig
Common Name: Brig ( Brigatinib
Targets:ALK, EGFR
First Approval in the U.S.:April 2017
First Approval in China: March 2022
Approved Indication: Crizotinib intolerance or ALK-positive metastatic NSCLC with disease progression after treatment, first-line treatment of ALK-positive NSCLC (China)
Specifications: 30mg*21, 30mg*180, 90mg*60
Recommended dose: Initial dose: 90 mg orally per day for the first 7 days. If the initial dose is tolerated within the first 7 days, the dose is increased to 180 mg orally once daily. Can be taken on an empty stomach or with meals.
Storage conditions: Room temperature 20°C~25°C
Clinical data
In this international multi-center phase III clinical trial A total of 275 patients with ALK-positive locally advanced or metastatic non-small cell lung cancer who had not received prior ALK inhibitor therapy were enrolled in the ALTA-1L trial (brigatinib-treated group, n=137; crizotinib). treatment group, n=138 cases).
In the brigatinib arm, the median age of patients was 58 years; 29% of patients had brain metastases at baseline; 26% of patients had prior chemotherapy for advanced or metastatic disease .
In the crizotinib arm, the median age of patients was 60 years; 30% of patients had brain metastases at baseline; 27% of patients had received prior chemotherapy for advanced or metastatic disease .
The primary endpoint of the study was progression-free survival (PFS); the secondary endpoints were overall objective response rate (ORR) and intracranial ORR.
According to the results of the ALTA-1L trial, for patients receiving brigatinib tablets, the median progression-free survival (PFS) assessed by the Independent Review Committee (IRC) reached 24 months , the median PFS for crizotinib in the control group was 11.1 months; the median PFS for both groups by investigator assessment was 30.8 months vs 9.2 months strong>.
In addition, the clinical efficacy of brigatinib in patients with brain metastases is also very prominent. In patients with brain metastases at baseline, the intracranial ORR of brigatinib vs crizotinib was 78% vs 26%; intracranial duration of slow response (DOR) was 27.9 months vs 9.2 months; intracranial median PFS was 24 months vs 5.6 months, significantly reduced the risk of disease progression or death by 75%; 4-year overall survival (OS) was 71% vs 44% compared to control crizotinib , Brigatinib reduced the risk of disease progression or death by 57%.
Chart Note: Data Summary of Targeted Drugs for First-Line Treatment of ALK-Positive Lung Cancer
Adverse Reactions
Safety In terms of sexuality, the adverse reactions of brigatinib are mostly mild and can be tolerated with long-term use.
In the ALTA-1L trial, serious adverse reactions occurred in 33% of patients treated with brigatinib. Besides disease progression, the most common serious adverse reactions included: interstitial pneumonia, pyrexia, dyspnoea, pulmonary embolism< /strong> and weak. Fatal adverse reactions other than disease progression occurred in 2.9% of patients, including pneumonia, cerebrovascular accident, and multiple organ dysfunction syndrome.
The most common adverse reactions of brigatinib in the ALTA-1L trial (≥10%) included: diarrhea, rash, Cough, hypertension, fatigue, nausea, myalgia, difficulty breathing< /strong>, abdominal pain, and headache.
Conclusion
ALTA-1L study showed that the clinical efficacy of brigatinib in the first-line treatment of patients with ALK-positive non-small cell lung cancer is better than that of crizotinib, especially in patients with brain metastases .
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