Brigatinib/brigatinib and alectinib produce similar PFS after crizotinib in non-small cell lung cancer

According to the researchers,Phase 3 data support brigatinib and alectinib as standard treatment options for patients with ALK-positive non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib. The researchers found that brigatinib and alectinib produced similar progression-free survival (PFS) in these patients. The trial (ClinicalTrials.gov identification number: NCT03596866) included 248 patients with ALK-positive non-small cell lung cancer who had previously been treated with crizotinib. Patients were randomly assigned to receive brigatinib 180 mg once daily (n=125) or alectinib 600 mg twice daily (n=123). Baseline characteristics were similar in both groups. The median follow-up times were 15.9 months in the brigatinib group and 16.9 months in the alectinib group.

Median PFS was 19.3 months in the brigatinib group and 19.2 months in the alectinib group (hazard ratio, 0.97; 95% CI, 0.66-1.42; P = .8672). The 1-year PFS rates of the brigatinib group and the alectinib group were 64% and 62% respectively. There were no differences in PFS between treatment groups based on smoking status, prior chemotherapy, baseline brain metastases, or other factors. Overall survival data are immature, but 1-year overall survival rates are estimated to be 89% in the brigatinib group and 96% in the alectinib group. The objective response rates (ORR) of the brigatinib group and the alectinib group were 52% and 61% respectively. The median duration of response (DOR) was 17.5 months and 20.2 months, respectively. The ORR in patients with brain metastases at baseline was 73% in the brigatinib group and 68% in the alectinib group. Neither treatment achieved the median duration of response in these patients.

There were at least 10 percentage points more treatment-related adverse events (TRAEs) in the brigatinib group than in the alectinib group, including increased creatine phosphokinase (70% vs. 29%), increased aspartate aminotransferase (53% vs. 38%), and hypertension (22% vs. 1%). TRAEs that were at least 10 percentage points more common with alectinib than with brigatinib were increased blood bilirubin (29% vs. 2%), constipation (23% vs. 2%), anemia (25% vs. 14%), and peripheral edema (13% vs. 2%). Overall, grade 3-4 TRAEs were more common in the brigatinib group than in the alectinib group (44% and 18%, respectively). There were no treatment-related deaths in either group.

Both treatments were pretreated with crizotinibRelated to the longest PFS reported to date in ALK+ NSCLC, these data support brigatinib and aletinib as standard treatment options for crizotinib-pretreated ALK+ NSCLC patients.