Current Results of Brigatinib in the Treatment of Lung Cancer
The results of the primary analysis showed a significant extension of PFS in patients with non-small cell lung cancer (NSCLC) treated with brigatinib compared to crizotinib. The recently published secondary analysis confirms these results.
Treatment Options for NSCLC
Non-small cell lung cancers with a mutation in the anaplastic lymphoma kinase gene (ALK+ NSCLC) occur in 2−5% of lung cancer cases. They are primarily found in adenocarcinomas, non-smokers or former light smokers, and younger patients.
Targeted therapy shows a higher frequency of treatment responses, extends progression-free survival (PFS), and overall survival (OS) compared to chemotherapy.
The first registered ALK inhibitor was crizotinib, followed by second-generation (alectinib, brigatinib, ceritinib) and third-generation (lorlatinib) agents, which have better blood-brain barrier penetration, reducing the incidence or progression of brain metastases. All ALK inhibitors are intended for oral administration.
Brigatinib and its Indications
Brigatinib is a tyrosine kinase inhibitor that blocks ALK, the oncogene C-ros (ROS1), and the insulin-like growth factor receptor (IGF-1R). Its efficacy has been demonstrated in patients with ALK and ROS1 gene rearrangements who were resistant to crizotinib. Brigatinib monotherapy is indicated for adult patients with advanced ALK+ NSCLC without prior ALK inhibitor treatment or patients with advanced ALK+ NSCLC after crizotinib treatment.
Methodology and Course of the ALTA-1L Study
ALTA-1L was a randomized open-label phase III registration study comparing the efficacy of brigatinib versus crizotinib in adult patients with locally advanced or metastatic NSCLC with a confirmed ALK gene mutation, who had not been previously treated with an ALK inhibitor. A total of 275 patients were enrolled in the study. They were randomized in a 1:1 ratio to receive brigatinib (90 mg once daily for the first 7 days, then 180 mg once daily) or crizotinib (250 mg twice daily). Stratification was based on the presence of brain metastases and prior chemotherapy administration. The brigatinib treatment continued until disease progression or unacceptable toxicity occurred.
Results
The median duration of response was 24.3 months for brigatinib treatment and 8.4 months for crizotinib treatment. The median progression-free survival (PFS, assessed by a blinded independent review committee − BIRC) was consistently higher in patients treated with brigatinib (24.0 months for brigatinib vs. 11.0 months for crizotinib; hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.35−0.68; p < 0.0001). The results were similar when assessed by the investigator (median PFS 29.4 vs. 9.2; HR 0.43; 95% CI 0.31–0.61). Brigatinib treatment provided better quality of life and extended the time to deterioration in overall health score compared to crizotinib (HR 0.70; 95% CI 0.49–1.00; p = 0.049).
In patients with brain metastases at study entry, brigatinib significantly extended intracranial PFS compared to crizotinib (24.0 vs. 5.6 months; HR 0.31; 95% CI 0.17–0.56; p < 0.0001).
No new safety risks were observed during the brigatinib treatment.
Conclusion
Brigatinib has demonstrated its superiority in the treatment of ALK-positive NSCLC compared to crizotinib, expanding the first-line treatment options for these patients, even in the presence of CNS metastases.
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Source: Černovská M. Brigatinib. Acta Medicinae 2021; 3: 104–106.
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