Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou.
ESMO Open. 2023 Jun;8(3):101560. doi: 10.1016/j.esmoop.2023.101560. Epub 2023 May 23.
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.
间变性淋巴瘤激酶 (ALK) 重排发生在约 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具有 ALK 重排的患者的治疗模式,与经典的铂类化疗相比,显著提高了客观缓解率、无进展生存期和总生存期。几种 ALK 酪氨酸激酶抑制剂 (ALK-TKIs),包括克唑替尼、阿来替尼、塞瑞替尼、布加替尼、恩沙替尼和劳拉替尼,已被推荐为晚期 NSCLC 患者 ALK 重排的标准一线治疗药物。ALK 重排的患者通常对 ALK-TKIs 表现出长期持久的反应;因此,在临床实践中,ALK-TKIs 的不良反应 (ADR) 管理对于最大限度地提高临床效益、防止对生活质量产生不利影响和提高患者依从性至关重要。一般来说,ALK-TKIs 具有良好的耐受性。然而,也有一些严重的毒性,可能需要调整剂量甚至停止治疗,并且 ALK-TKIs 的 ADR 管理变得越来越重要。由于目前在中国尚无关于管理 ALK-TKIs 引起的 ADR 的相关指南或共识建议,因此这类药物的治疗应用仍存在一定风险。为了改善 ALK-TKIs 相关 ADR 的临床管理,中国临床肿瘤学会 (CSCO) 非小细胞肺癌专业委员会牵头讨论并总结了 ALK-TKIs 引起的 ADR 的发生率、诊断和分级标准以及预防和治疗。