Real-World Outcomes of Brigatinib Compared to Alectinib as a Second-Line Therapy After Crizotinib in Advanced Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer Patients.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.