Real-World Outcomes of Brigatinib Compared to Alectinib as a Second-Line Therapy After Crizotinib in Advanced...

Second-generation anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and brigatinib, are widely used in patients with ALK-positive non-small cell lung cancer (NSCLC) who develop resistance or progress on crizotinib. However, real-world data comparing their efficacy and safety remain limited. This multicenter, prospective cohort study compared the clinical outcomes of alectinib and brigatinib in this setting.

Patients with stage IV ALK-positive NSCLC who progressed on crizotinib were enrolled and treated with either brigatinib or alectinib. The primary endpoint was the progression-free survival (PFS) rate.

Sixty patients were included (brigatinib, n = 34; alectinib, n = 26). Median follow-up durations were 26.5 and 30.0 months. Disease progression or death occurred in 50.0% (brigatinib) and 46.2% (alectinib), respectively. The 3-year PFS was 51.5% (brigatinib) vs. 62.1% (alectinib), with no significant difference at 5 years (40.0% vs. 42.5%; p = 0.260). Overall response rates were similar (58.8% vs. 46.2%; p = 0.475). However, intracranial outcomes appeared more favorable with alectinib: the 3-year intracranial PFS was 70.5% vs. 31.7% (p = 0.023), and intracranial ORR was 94.4% vs. 64.3% (p = 0.028). More patients in the brigatinib group had prior whole-brain radiotherapy (21.4% vs. 5.6%), while radiosurgery was more frequent in the alectinib group (55.6% vs. 35.7%). Treatment discontinuation rates due to adverse events were comparable between the two groups.

In crizotinib-refractory ALK-positive NSCLC, systemic efficacy was not significantly different between brigatinib and alectinib; however, alectinib was associated with more favorable intracranial PFS and ORR, which may be partly explained by differences in prior brain-directed local treatments.