Alectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: final overall survival analysis of the phase III ALEX study

作者：Solange Peters, D. Ross Camidge, Rafał Dziadziuszko, Shirish M. Gadgeel, A. Shaw, Dong‐Wan Kim, M. Pérol, Rafael Rosell, Parneet Cheema, Dong-Jun Lim, J.J. Lin, Nick Pavlakis, J.S. Ahn, Li Zhang, Volkmar Henschel, A.A. Higgerson, V. McNally, Isabelle Rooney, Astrid Scalori, Vlatka Smoljanović, T. Mok · 发表于：Annals of Oncology · 年份：2025 · DOI：10.1016/j.annonc.2025.09.018 · 被引用次数：20 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Lung Cancer Research Studies

BACKGROUND: ALEX, a global, randomized, phase III trial evaluated alectinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). This final analysis provides mature overall survival (OS), duration of response (DOR) and long-term safety data. PATIENTS AND METHODS: Treatment-naïve patients with stage III/IV ALK-positive NSCLC were randomly assigned to receive alectinib [600 mg twice daily (b.i.d.)] or crizotinib (250 mg b.i.d.) until disease progression, unacceptable toxicity, withdrawal, or death. Primary endpoint was investigator-assessed progression-free survival (previously reported). Key secondary endpoints included OS, DOR and safety. RESULTS: A total of 303 patients (alectinib, n = 152; crizotinib, n = 151) were enrolled. At the updated data cut-off (28 April 2025), after a median follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 [95% confidence interval (CI) 62.3 months-not estimable] versus 54.2 (95% CI 34.6-75.6 months) months, respectively [hazard ratio (HR) 0.78; 95% CI 0.56-1.08]. Improvement in median OS was observed with alectinib in patients with and without central nervous system (CNS) metastases at baseline [with CNS metastases: 63.4 (n = 59) versus 30.9 (n = 53) months with alectinib versus crizotinib, respectively (HR 0.68; 95% CI 0.40-1.15); without CNS metastases: 94.0 (n = 93) versus 69.8 (n = 98) months (HR 0.87; 95% CI 0.58-1.32)]. Median DOR in confirmed responders was longer with ale...