Brigatinib in the Therapy of ALK-Positive NSCLC in Patients Refractory to Crizotinib Therapy – Results of the Final Analysis of Clinical Studies
Previously published results of clinical studies have shown that in patients refractory to crizotinib therapy, the administration of brigatinib led to a high rate of therapeutic response (systemic and intracranial) and simultaneously improved median progression-free survival. Additional results presented at this year's ASCO congress included the final outcomes of studies focusing on the administration of brigatinib specifically in patients refractory to crizotinib therapy.
NSCLC Refractory to Targeted Therapy
Anaplastic lymphoma kinase (ALK) inhibitors are a standard therapy for patients with non-small cell lung cancer (NSCLC) with ALK gene rearrangement. Brigatinib is an ALK inhibitor with broad activity against mutations causing resistance to crizotinib therapy.
The presented poster included an assessment of the long-term efficacy and safety of brigatinib administration as part of the final analysis of phase I/II and phase II ALTA clinical studies over periods of > 5 years and > 4 years from the last patient entering the evaluation, respectively.
Study Results
The safety profile of brigatinib was consistent with previous results, and no new safety risks were reported in the final analysis.
Phase I/II Study
The phase I/II clinical study evaluated various dosing regimens of brigatinib in 79 patients with ALK-positive NSCLC (71 of them with a history of prior crizotinib therapy). Ten patients received brigatinib until the end of the study, spanning a period of 5.6 years from the last patient enrollment. In this study, the median progression-free survival (PFS) for all patients was 14.5 months, the median overall survival (OS) was 47.6 months, and the probability of 5-year overall survival was 42%.
For the 71 patients with a history of prior crizotinib therapy, PFS with brigatinib was 13.4 months (95% confidence interval [CI] 9.2–16.7), the median OS was 30.1 months (95% CI 21.4–55.0), and the 5-year overall survival probability was 35%.
ALTA Clinical Study
In the ALTA phase II clinical study, patients with ALK-positive NSCLC who had progressed on crizotinib therapy were randomized 1:1 to receive brigatinib at daily doses of 90 mg and 180 mg (with a 7-day lead-in dose of 90 mg). Administration of brigatinib at a daily dose of 180 mg was associated with higher overall response rates (ORR), PFS, and OS compared to the 90 mg daily dose group.
In the higher dose brigatinib group, an independent review committee determined an ORR of 56%, a median duration of response (DoR) of 15.7 months, a median PFS of 16.7 months, a median OS of 40.6 months, and a 5-year OS probability of 43%. For patients with baseline brain metastases, the independent committee reported an intracranial overall response rate of 67%, with a median intracranial DoR of 16.6 months and a median intracranial PFS of 18.4 months.
Conclusion
The final analysis of the phase I/II clinical study and the ALTA clinical study indicated that brigatinib demonstrated long-term sustained activity and a consistent safety profile in patients with ALK-positive NSCLC refractory to crizotinib, aligning with previous study results.
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Source: Gettinger S. N., Huber R. M., Kim D-W. et al. Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): final results of the phase 1/2 and phase 2 (ALTA) trials. J Clin Oncol 2021; 39 (15_suppl.): 9071, doi: 10.1200/JCO.2021.39.15_suppl.9071.
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