First-Line Alectinib Versus Ceritinib With or Without Brain Radiotherapy in ALK-Positive Non-Small Cell Lung Cancer with Brain Metastases: A Real-World Multicenter Study from Vietnam.

Abstract

Background: This study compared the efficacy of first-line alectinib versus ceritinib and evaluated the role of upfront brain radiotherapy (RT) in patients with ALK-positive non-small cell lung cancer (NSCLC) and brain metastases (BM).

Methods: We retrospectively analyzed 108 patients with ALK-positive NSCLC and baseline BM treated with first-line alectinib (n = 42) or ceritinib (n = 66) at two Vietnamese centers between 2019 and 2025. Intracranial and systemic responses were assessed by RANO-BM and RECIST v1.1 criteria, respectively. Survival outcomes were analyzed using the Kaplan-Meier method and multivariable Cox regression.

Results: First-line alectinib demonstrated superior intracranial disease control compared with ceritinib (iDCR 97.6% vs. 83.3%, p = 0.026; median iPFS 40.4 vs. 17.2 months, univariable HR 0.46, 95% CI 0.26-0.82, p = 0.005). Systemic PFS was also significantly longer with alectinib (35.9 vs. 11.5 months, univariable HR 0.38, 95% CI 0.22-0.65, p = 0.001). Exploratory subgroup analyses suggested differential effects of upfront brain RT by TKI, but interaction tests were non-significant (p = 0.642 for iPFS, p = 0.837 for systemic PFS). In multivariable analysis, alectinib remained an independent predictor of better iPFS (HR 0.38, 95% CI 0.20-0.70, p = 0.002) and systemic PFS (HR 0.34, 95% CI 0.20-0.59, p = 0.001). Grade ≥ 3 adverse events occurred in 19.0% of patients with alectinib versus 34.8% with ceritinib (p = 0.068).

Conclusions: In this real-world Vietnamese cohort, first-line alectinib showed superior intracranial and systemic efficacy over ceritinib. In resource-limited settings, ceritinib combined with upfront brain RT is a reasonable clinical alternative. The differential benefit of brain RT between the two TKIs remains hypothesis-generating.