Brigatinib in Patients With Crizotinib-Refractory ALK–Positive NSCLC
Treatment with brigatinib resulted in substantial whole-body and intracranial responses, as well as robust progression-free survival in a group of patients with anaplastic lymphoma kinase (ALK) gene–rearranged non–small-cell lung cancer (ALK-positive NSCLC), who were resistant to crizotinib, according to the results of a randomized phase II trial conducted by Dong-Wan Kim, MD, of Seoul National University Hospital, and colleagues and reported in the Journal of Clinical Oncology.
Most ALK-positive NSCLC patients treated with crizotinib eventually experience disease progression. Based on this rationale, the investigators sought to evaluate the efficacy of two regimens of brigatinib, an investigational next-generation ALK inhibitor, in 219 patients with crizotinib-refractory ALK-positive NSCLC.
Patients were stratified by the presence of brain metastases and best response to crizotinib and were randomly assigned (1:1) to 90 mg of oral brigatinib once daily (arm A: n=109) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B: n=110).
The investigator-assessed objective response rate after 8-month median follow-up was 45% in arm A and 54% in arm B. The researchers determined that the 180-mg dose with lead-in showed consistently better efficacy than the 90-mg dose, with acceptable safety. Common treatment-related adverse events were grades 1 and 2 nausea, diarrhea, headache, and cough.