Thoracic Cancer · Published 2026-06-01 · DOI 10.1111/1759-7714.70325
Hoang Gia Nguyen, Xuan Hau Nguyen, Phuong Thi Bich Nguyen, Thu Huong Nguyen, Quang Bui Vinh
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.
Abstract from DOAJ. Public domain (CC0 1.0).
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Nguyen, H., Nguyen, X., Nguyen, P., et al. (2026). 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. Thoracic Cancer. https://doi.org/10.1111/1759-7714.70325