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.
BMC Cancer. 2021 Mar 24;21(1):309. doi: 10.1186/s12885-021-08005-1.
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.
Sixty-five ALK-positive advanced NSCLC patients receiving second-generation ALK inhibitors following treatment failure of crizotinib were retrospectively analyzed for the therapeutic efficacy.
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.
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.
克唑替尼是治疗间变性淋巴瘤激酶（ALK）融合的晚期非小细胞肺癌（NSCLC）的标准治疗方法。克唑替尼治疗失败常涉及药物不耐受或耐药。在这种情况下，比较使用第二代 ALK 抑制剂的效果仍缺乏研究。
对 65 例接受克唑替尼治疗后进展的 ALK 阳性晚期 NSCLC 患者接受第二代 ALK 抑制剂治疗的疗效进行回顾性分析。
43 例（66.2%）和 22 例（33.8%）患者分别接受阿来替尼和塞瑞替尼治疗。与塞瑞替尼相比，阿来替尼治疗：12 个月无进展生存率（PFS）率（61.0%[95%置信区间，47.1%至 78.9%] vs. 54.5%[95%CI，37.3%至 79.9%]）；疾病进展或死亡的风险比（HR）为 0.61（95%CI，0.31-1.17；p=0.135）。多因素 Cox 回归显示 ECOG PS（0-1 与 2-3，HR 0.09[95%CI，0.02-0.33]；p<0.001）和克唑替尼治疗失败的原因（耐药与不耐受，HR 2.75[95%CI，1.26-5.99]；p=0.011）是第二代 ALK 抑制剂 PFS 的独立预测因素。与塞瑞替尼相比，阿来替尼治疗与 CNS 进展发生率较低相关（原因特异性 HR，0.10[95%CI，0.01-0.78]；p=0.029），且在克唑替尼治疗失败原因是不耐受的患者中疗效更高（HR 0.29[95%CI，0.08-1.06]；p=0.050）。最常见的不良事件是阿来替尼治疗的 10 例（23.3%）患者的 AST/ALT 升高和塞瑞替尼治疗的 8 例（36.4%）患者的腹泻。
克唑替尼治疗后使用第二代 ALK 抑制剂疗效满意。阿来替尼治疗在选定的克唑替尼治疗失败患者中具有 CNS 保护作用和更高的 PFS。
