A rearrangement of the anaplastic lymphoma kinase (ALK) gene occurs in about 5% of NSCLC patients. Although the first ALK inhibitor Crizotinib (Xalkori®) induces initial responses in ALK-positive NSCLC patients, most patients ultimately develop resistance due to acquired ALK mutations and the low permeability of the central nervous system (CNS). To investigate the activity and safety of Brigatinib, a next-generation ALK inhibitor, researchers constructed a phase 1/2 study (NCT01449461) that enrolled 137 NSCLC patients. The objective response rate was 62%, including 4 complete and 40 partial responses among 71 ALK-positive patients previously treated with Crizotinib, and the median progression free survival was 13.2 months. Besides, all 8 patients without previous Crizotinib treatment achieved an objective response. Moreover, there were 3 intracranial response cases among 6 CNS metastasis patients. In conclusion, Brigatinib demonstrated favorable activity in ALK-positive NSCLC patients, including Crizotinib-treated, Crizotinib naïve and brain metastasis patients. These results indicate that Brigatinib may become a new therapeutic option for ALK-positive NSCLC.
Gettinger SN., et al., Lancet Oncol. 17:1683-1696, 2016. DOI: 10.1016/S1470-2045(16)30392-8.