Shanghai R&D Center, Jiangsu Simcere Pharmaceutical Co., Ltd., Shanghai 201318, P.R. China.
Oncol Rep. 2021 Jan;45(1):13-28. doi: 10.3892/or.2020.7851. Epub 2020 Nov 13.
Since the discovery of targeted therapy with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have been introduced as the first‑line treatment for non‑small cell lung cancer (NSCLC) patients who carry sensitizing ALK‑activating mutations. Compared with conventional chemotherapeutic regimens, small‑molecule ALK‑TKIs exhibit excellent clinical efficacy in ALK‑positive NSCLC. A series of studies have indicated that ALK‑TKI agents as the first‑line treatment, including crizotinib, ceritinib, brigatinib, alectinib and entrectinib, can benefit patients with ALK‑positive NSCLC. However, resistance to ALK‑TKIs has emerged. ALK‑TKIs are associated with significantly disabling and undesirable effects that adversely impact quality of life and compliance. This study reviews the pharmacodynamics, efficacy and safety of ALK‑TKI agents in order to summarize these effects as well as the relevant management strategies. It is worth emphasizing that the frequency and severity of an adverse effect often varies across different trials.
自发现表皮生长因子受体(EGFR)靶向治疗以来,间变性淋巴瘤激酶(ALK)酪氨酸激酶抑制剂(TKI)已被作为携带敏感 ALK 激活突变的非小细胞肺癌(NSCLC)患者的一线治疗药物。与传统化疗方案相比,小分子 ALK-TKI 在 ALK 阳性 NSCLC 中具有优异的临床疗效。一系列研究表明,ALK-TKI 药物作为一线治疗药物,包括克唑替尼、塞瑞替尼、布加替尼、阿来替尼和恩曲替尼,可使 ALK 阳性 NSCLC 患者获益。然而,已经出现了对 ALK-TKI 的耐药性。ALK-TKI 与显著的致残和不良影响相关,会对生活质量和依从性产生不利影响。本研究综述了 ALK-TKI 药物的药效学、疗效和安全性,以总结这些影响以及相关的管理策略。值得强调的是,不良事件的频率和严重程度在不同试验中往往存在差异。