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 - 2021
Chih-Hsi S. Kuo1, Pi‐Hung Tung1, Allen Chung‐Cheng Huang1, Chin‐Chou Wang2, John Wen‐Cheng Chang3, Chien‐Ying Liu1, Fu‐Tsai Chung1, Yueh‐Fu Fang1, Yike Guo4, Cheng‐Ta Yang1
1Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan City, Taiwan
2Department of Computing, Imperial College London, Data Science Institute, London, UK
3Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
4Department of Medical Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan

Tóm tắt

Abstract Background Crizotinib 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. Methods Sixty-five ALK-positive advanced NSCLC patients receiving second-generation ALK inhibitors following treatment failure of crizotinib were retrospectively analyzed for the therapeutic efficacy. Results Forty-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. Conclusion Second-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.

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