Brigatinib has shown substantial clinical activity among patients with ALK-positive non-small cell lung cancer (NSCLC) who have brain metastases, according to results from both an ongoing Phase 1/2 trial (ClinicalTrials.gov identifier: NCT01449461) and ALTA, a Phase 2 ongoing trial (ClinicalTrials.gov identifier: NCT02094573), according to results presented at the International Association for the Study of Lung Cancer (IASLC) 17th Annual World Conference on Lung Cancer in Austria.1
Patients with NSCLC who are treated with crizotinib, an ALK and ROS1 inhibitor, often have disease progression in the brain. Brigatinib is an investigational next-generation ALK inhibitor that is being evaluated in several ongoing trials.
In the Phase 1/2 trial (Ph1/2), patients with advanced malignancies, including ALK-positive NSCLC, received 30-300 mg of brigatinib per day. In ALTA, patients with crizotinib-resistant advanced ALK-positive NSCLC received 90 mg per day (arm A) or 180 mg per day with a 7-day lead-in at 90 mg (arm B).
In Ph1/2, 50 out of 79 (63%) patients with ALK-positive NSCLC had baseline brain metastases. Median age was 53 years, 76% had received prior chemotherapy, and 8% were crizotinib-naive. As of November 16, 2015, 25 of 50 (50%) patients were receiving brigatinib. Among those with non-measurable lesions (31 patients), 35% had confirmed complete resolution of lesions. For those with baseline brain metastases, median intracranial progression-free survival (PFS) was 15.6 months (46 patients).
In ALTA, 154 out of 222 (69%) of patients with ALK-positive NSCLC had baseline brain metastases. Median age was 52 years and 75% had received prior chemotherapy. As of February 29, 2016, 101 of 154 (66%) patients were receiving brigatinib. Among patients with non-measurable lesions, 7% in arm A and 18% in arm B had confirmed complete resolution.
RELATED: Smoking Cessation at any Age May Reduce Mortality Risk
For evaluable patients with baseline brain metastases, median intracranial PFS was 15.6 months in arm A (80 patients) and 12.8 months in arm B (73 patients).
- Gettinger SN, Kim D, Tiseo M, et al. Brigatinib activity in patients with ALK+ NSCLC and intracranial CNS metastases in two clinical trials. Paper presented at: International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer; December 2016; Vienna, Austria.