Camidge DR, et al. - This is a trial of brigatinib, a next-generation anaplastic lymphoma kinase gene (ALK) inhibitor, in patients with ALK-rearranged non–small-cell lung cancer (ALK-positive NSCLC) with brain metastases. Substantial intracranial responses and durable intracranial progression-free survival (iPFS) was seen to have resulted from treatment with brigatinib in ALK-positive, crizotinib-treated NSCLC. Patients receiving 180 mg per day (with lead-in) were found to have highest iPFS.

Methods

• In a phase I/II trial (phI/II), brigatinib (90 to 240 mg total daily) was administered to patients with ALK-positive NSCLC.
• In the subsequent randomized phase II trial ALTA (ALK in Lung Cancer Trial of AP26113), 90 mg once daily was given to patients in arm A; patients in arm B received 180 mg daily with 7-day lead-in at 90 mg.
• Primary end points (systemic objective response rates [ORRs]) were previously reported.
• Intracranial efficacy in patients with baseline brain metastases was evaluated by independent review committees.

Results

• Baseline brain metastases (50 of 79 [63%] were detected in most patients with ALK-positive NSCLC, phI/II; 80 of 112 [71%] and 73 of 110 [66%] in ALTA arms A and B, respectively), many of whom had no prior brain radiotherapy (23 of 50 [46%], phI/II; 32 of 80 [40%], ALTA arm A; 30 of 73 [41%], arm B).
• Crizotinib had been received by all patients, except four in phI/II.
• Intracranial ORR was confirmed to be 53% (eight of 15; 95% CI, 27% to 79%) in phI/II, 46% (12 of 26; 95% CI, 27% to 67%) in ALTA arm A, and 67% (12 of 18; 95% CI, 41% to 87%) in arm B, among patients with measurable (≥ 10 mm) brain metastases.
• In subsets without prior radiation or progression postradiation, similar intracranial ORRs were reported.
• The observed median intracranial progression-free survival (iPFS) among patients with any baseline brain metastases was 14.6 months (95% CI, 12.7 to 36.8 months), phI/II; 15.6 months (95% CI, 9.0 to 18.3 months), ALTA arm A; 18.4 months (95% CI, 12.8 months to not reached), ALTA arm B.