Brigatinib in the Therapy of ALK-Positive NSCLC – First Results of the J-ALTA Study
Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor with broad and potent activity against ALK gene mutations causing resistance to ALK inhibitor therapy (ALKi). In patients refractory to crizotinib therapy, brigatinib administration in phase III clinical trials led to high systemic and intracranial therapeutic responses and concurrently improved median progression-free survival (PFS). The primary analysis objective of the phase II J-ALTA clinical study, presented at this year's American Society of Clinical Oncology (ASCO) congress, was to assess the efficacy and safety of therapy in patients with ALK-positive NSCLC naïve to previous ALKi therapy.
Evaluated Patient Population
The J-ALTA study included a total of 104 patients. Thirty-two patients with a median follow-up duration of 14.2 months (3–19 months) were enrolled in the expansion cohort of the study, which represented patients naïve to ALK inhibitor therapy, with 27 of them undergoing brigatinib therapy at the time of primary analysis processing.
Study participants received brigatinib at a dose of 180 mg once daily (after an initial phase of therapy consisting of a 7-day introductory dose of 90 mg once daily). The median number of treatment cycles was 15 (1 cycle = 1 month; range 1–22 cycles), with all except 1 patient undergoing ≥ 6 cycles of treatment.
Primary Analysis Results
In the primary analysis, the 1-year overall survival probability was determined to be 97% (95% confidence interval [CI] 79.8–99.6) with 2 complete treatment responses and 29 partial responses. The 12-month intracranial progression-free survival rate according to modified RECIST v1.1 criteria assessed by an independent committee was 93% (95% CI 75–98). Sufficient data were not available to determine the median duration of treatment response by the independent committee. The median best therapeutic response in target lesions assessed by the independent committee was –72%.
The safety profile of brigatinib was consistent with the profile observed in the phase III ALTA-1 study, which was used to compare demographic and baseline characteristics and treatment-related adverse events (TEAEs). At the time of primary analysis processing, no case of treatment discontinuation due to TEAEs was observed.
Conclusion
The primary analysis results of the J-ALTA study expansion cohort support the use of brigatinib in the first-line treatment of patients with ALK-positive NSCLC naïve to prior ALK inhibitor therapy.
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Source: Kondo M., Sugawara S., Yokoyama T. et al. Brigatinib in Japanese patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC): first results from the J-ALTA tyrosine kinase inhibitor (TKI)-naive expansion cohort. J Clin Oncol 2021; 39 (15_suppl.): 9042, doi: 10.1200/JCO.2021.39.15_suppl.9042.
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