Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt.
Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Crit Rev Oncol Hematol. 2019 Feb;134:56-64. doi: 10.1016/j.critrevonc.2018.11.004. Epub 2018 Dec 1.
Oral tyrosine kinase inhibitors targeting the chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) in non-small cell lung cancer (NSCLC) were associated with superior clinical outcome. Tyrosine Kinase inhibitors (TKIs) are known to have peculiar toxicity profile, hence, increasing awareness to the safety profile of ALK inhibitors is essential.
A comprehensive systematic review of literature has been conducted to include prospective trials that used the ALK inhibitors Crizotinib, Ceritinib, Alectinib, Brigatinib and Lorlatinib in patients with advanced NSCLC and have available efficacy and toxicity results.
A total of 14 studies including 2793 patients were considered eligible for our review and included two phase IB, seven phase II and five phase III studies. The most common adverse events (AEs) observed with ALK inhibitors were gastrointestinal (GI) toxicities as nausea (up to 83%), vomiting (up to 67%) and diarrhea (up to 86%), elevation of liver enzymes occurred in up to 60% and fatigue (up to 43%). There were differences in the toxicity patterns between the different ALK inhibitors with more GI and hepatic toxicities with Ceritinib, more visual disorders with Crizotinib, more dysgeusia with crizotinib and Alectinib and possibly more respiratory complications with Brigatinib. Most of the AEs were low grade and treatment-related deaths were associated with ALK inhibitors in 0-1% of patients.
Most of adverse effects of ALKi can be managed efficiently via dose modifications or interruptions. Timely identification of each ALKi pattern of toxicity can prevent treatment-related morbidity and mortality in this palliative setting.
针对非小细胞肺癌（NSCLC）中染色体重排间变性淋巴瘤激酶基因（ALK）的口服酪氨酸激酶抑制剂与更好的临床结局相关。已知酪氨酸激酶抑制剂（TKIs）具有特殊的毒性特征，因此，提高对 ALK 抑制剂安全性特征的认识至关重要。
对文献进行了全面的系统评价，纳入了使用 ALK 抑制剂克唑替尼、塞瑞替尼、阿来替尼、布加替尼和劳拉替尼治疗晚期 NSCLC 患者的前瞻性试验，并具有可用的疗效和毒性结果。
共有 14 项研究，包括 2793 名患者，被认为符合我们的综述标准，其中包括两项 I 期 B 研究、七项 II 期研究和五项 III 期研究。ALK 抑制剂最常见的不良反应（AE）是胃肠道（GI）毒性，包括恶心（高达 83%）、呕吐（高达 67%）和腹泻（高达 86%），肝酶升高高达 60%，疲劳（高达 43%）。不同的 ALK 抑制剂之间存在毒性模式的差异，塞瑞替尼的 GI 和肝毒性更多，克唑替尼的视觉障碍更多，克唑替尼和阿来替尼的味觉障碍更多，布加替尼可能的呼吸系统并发症更多。大多数 AE 为低级别，与 ALK 抑制剂相关的治疗相关死亡在 0-1%的患者中发生。
大多数 ALKi 的不良反应可以通过剂量调整或中断来有效管理。及时识别每种 ALKi 的毒性模式可以防止在姑息治疗环境中发生与治疗相关的发病率和死亡率。
