Real-world comparative outcomes of alectinib and brigatinib in ALK-positive non–small cell lung cancer: A retrospective cohort analysis using HIRA data.

Abstract

8608 Background: Alectinib and brigatinib are both recommended as first-line treatments for patients with ALK-positive non–small cell lung cancer (NSCLC). However, direct real-world comparisons of these agents remain limited. Methods: We retrospectively reviewed patients diagnosed with ALK-positive NSCLC between 2007 and 2023 who did not undergo surgical resection. Among these, 1,009 patients received either alectinib (n=868) or brigatinib (n=141) as first-line therapy on HIRA data. Baseline characteristics, comorbidities (e.g., diabetes, hypertension), and outcomes—including overall survival (OS) and progression-free survival (PFS)—were collected. Cox proportional hazards models adjusted for age ≥70 years, sex, and comorbidities were used to estimate hazard ratios (HRs) for death and disease progression. Results: The mean age was 61.56 years (SD 13.72), and 49.45% of patients were male. Patients receiving alectinib were older on average (p<0.001), but no significant differences in major comorbidities were observed between the two groups. In unadjusted analyses, brigatinib was associated with a lower risk of death compared with alectinib (HR 0.60, 95% CI 0.40–0.90; p=0.013), but this association was not significant after multivariable adjustment (HR 0.69, 95% CI 0.46–1.03; p=0.07). Conversely, alectinib was associated with significantly longer first and second PFS compared with brigatinib (1st PFS HR 1.53, p=0.012; 2nd PFS HR 4.02, p<0.001). Both alectinib- and brigatinib-treated patients who transitioned to lorlatinib demonstrated notably prolonged survival. Conclusions: In this real-world study, both alectinib and brigatinib provided favorable survival outcomes in patients with ALK-positive NSCLC. While brigatinib showed a trend toward reduced mortality in univariable analysis, this was not maintained in adjusted models. Alectinib conferred a longer duration of disease control (PFS) in both first- and second-line settings. Further prospective studies are warranted to clarify the optimal sequencing of ALK inhibitors and to validate these findings.