间变性淋巴瘤激酶(ALK)重排发生在3%-6%的晚期非小细胞肺癌(NSCLC)患者中。有效抑制ALK基因的小分子药物彻底改变了ALK重排患者的治疗模式,显著提高客观反应率,无进展生存期,和与经典铂类化疗相比的总生存率。几种ALK酪氨酸激酶抑制剂(ALK-TKIs),包括克唑替尼,阿列替尼,ceritinib,布加替尼,ensartinib,和lorlatinib,已被推荐为ALK重排的晚期NSCLC患者的标准一线治疗。ALK重排患者通常表现出对ALK-TKIs的长期持久反应;因此,使用ALK-TKIs管理药物不良反应(ADR)在临床实践中至关重要,以最大程度地提高临床效益,防止对生活质量的不利影响,提高患者的依从性。总的来说,ALK-TKIs耐受性良好。有,然而,一些可能需要调整剂量甚至停止治疗的严重毒性以及ALK-TKIs治疗ADR的重要性日益增加.此类药物的治疗用途仍然存在一定的风险,因为目前在中国没有相关的指南或共识建议来管理ALK-TKIs引起的ADR。为了提高ALK-TKIs不良反应的临床管理水平,由中国临床肿瘤学会(CSCO)非小细胞肺癌专业委员会牵头,诊断和分级标准,以及ALK-TKIs引起的ADRs的预防和治疗。
Anaplastic lymphoma kinase (ALK) rearrangements occur in ∼3%-6% of patients with advanced non-small-cell lung cancer (NSCLC). Small molecular drugs that effectively inhibit ALK gene have revolutionized the therapeutic paradigm for patients with ALK rearrangements, resulting in significant improvements in objective response rate, progression-free survival, and overall survival compared with classical platinum-based chemotherapy. Several ALK tyrosine kinase inhibitors (ALK-TKIs), including crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib, have been recommended as standard first-line treatment for advanced NSCLC patients with ALK rearrangements. Patients with ALK rearrangements typically exhibit long-term durable responses to ALK-TKIs; therefore, the management of adverse drug reactions (ADRs) with ALK-TKIs is crucial in clinical practice to maximize clinical benefits, prevent an adverse impact on quality of life, and improve patient compliance. In general, ALK-TKIs are well tolerated. There are, however, a number of serious toxicities that may necessitate dose modification or even discontinuation of treatment and the management of ADRs with ALK-TKIs has grown in importance. The therapeutic use of this class of medications still carries some risk because there are currently no pertinent
guidelines or
consensus recommendations for managing ADRs caused by ALK-TKIs in China. In order to improve the clinical management of ADRs with ALK-TKIs, the Chinese Society of Clinical Oncology (CSCO) Non-small Cell Lung Cancer Professional Committee led the discussion and summary of the incidence, diagnosis and grading standards, and prevention and treatment of ADRs caused by ALK-TKIs.