A retrospective study of alectinib versus ceritinib in patients with advanced non–small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed

BMC Cancer

Chin-Chou Wang¹  Yi-Ke Guo²  John Wen-Cheng Chang³  Yueh-Fu Fang⁴  Fu-Tsai Chung⁴  Cheng-Ta Yang⁴  Allen Chung-Cheng Huang⁴  Chien-Ying Liu⁴  Pi-Hung Tung⁴  Chih-Hsi Scott Kuo⁵ 

[1] Department of Computing, Imperial College London, Data Science Institute, London, UK;Department of Medical Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan;Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan City, Taiwan;Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan City, Taiwan;Department of Medical Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan;

关键词: NSCLC;    ALK;    Crizotinib;    Treatment failure;    Alectinib;    Ceritinib;    CNS;   

DOI  :  10.1186/s12885-021-08005-1

来源: Springer

【 摘 要 】

BackgroundCrizotinib is the approved treatment for advanced non-small cell lung cancers (NSCLCs) of anaplastic lymphoma kinase (ALK) fusion. Failure of crizotinib treatment frequently involves drug intolerance or resistance. Comparison of using second-generation ALK inhibitors in this setting remains lacking.MethodsSixty-five ALK-positive advanced NSCLC patients receiving second-generation ALK inhibitors following treatment failure of crizotinib were retrospectively analyzed for the therapeutic efficacy.ResultsForty-three (66.2%) and 22 (33.8%) patients received alectinib and ceritinib, respectively. Comparing alectinib to ceritinib treatment: the 12-month progression-free survival (PFS) rate (61.0% [95% confidence interval, 47.1 to 78.9%] vs. 54.5% [95% CI, 37.3 to 79.9%]); the hazard ratio (HR) for disease progression or death, 0.61 (95% CI, 0.31–1.17; p = 0.135). Multivariate Cox regression showed ECOG PS (0–1 vs. 2–3 HR 0.09 [95% CI, 0.02–0.33]; p < 0.001) and cause of crizotinib treatment failure (resistance vs. intolerance HR 2.75 [95% CI, 1.26–5.99]; p = 0.011) were the independent predictors for the PFS of second-generation ALK inhibitors. Treatment of alectinib, compared to ceritinib, was associated with a lower incidence of CNS progression (cause-specific HR, 0.10; 95% CI 0.01–0.78; p = 0.029) and a higher efficacy in patients whose cause of crizotinib treatment failure was intolerance (HR 0.29 [95% CI, 0.08–1.06]; p = 0.050). The most commonly noted adverse events were elevated AST/ALT in 10 (23.3%) patients treated with alectinib and diarrhea in 8 (36.4%) patients treated with ceritinib.ConclusionSecond-generation ALK inhibitors in crizotinib-treated patients showed a satifactory efficacy. Alectinib treatment demonstrated a CNS protection activity and a higher PFS in selected patients failing crizotinib treatment.

【 授权许可】

CC BY