Currently, six ALK inhibitors (including crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib) have been approved for first-line treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), yet clinical decision-making remains challenging.

This study aimed to comprehensively evaluate these six ALK inhibitors across five dimensions (safety, efficacy, pharmaceutical properties, drug economy, and other properties) to provide evidence-based support for clinical drug selection.

Data were sourced from drug labels, guidelines by the National Comprehensive Cancer Network (NCCN), Chinese Society of Clinical Oncology (CSCO), and European Society for Medical Oncology (ESMO), network meta-analyses, as well as authoritative platforms including Zhejiang Provincial Two-Designated Healthcare Security Information Database, the National Healthcare Security Administration Information Database, and the National Medical Products Administration Drug Evaluation Center, covering information essential for evaluating drug efficacy, safety, and pricing. Based on the Rapid Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (2nd Edition), a comprehensive evaluation system comprising five dimensions (safety, efficacy, pharmaceutical properties, drug economy, and other properties) was developed using the Delphi method to assess six ALK inhibitors (including crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib). A nine-member expert panel with senior titles and over five years of relevant experience conducted six discussion rounds to finalize evaluation criteria (three rounds to define items and three to assign weights). Final scoring and statistical analysis were performed independently by a two-author team according to the established standards.

The overall ranking of the six ALK inhibitors was: brigatinib (85.5 points) >alectinib (82.7 points) >lorlatinib (82.2 points) >ensartinib (78.8 points) >ceritinib (77.4 points) >crizotinib (76.5 points). Alectinib scored highest in the core dimensions (safety, efficacy, and pharmaceutical properties) (71.0 points). Generational trend analysis revealed that second-generation inhibitors outperformed third-generation and first-generation drugs (except for ceritinib and ensartinib), while in core dimensions, third-generation inhibitors scored higher than second-generation and first-generation drugs (except for alectinib and ceritinib).

This study demonstrates that different ALK inhibitors exhibit distinct advantages across the five evaluated dimensions. Brigatinib achieved the highest overall score, while alectinib ranked highest in core dimensions. Second- and third-generation drugs generally performed better, providing valuable evidence for individualized treatment selection based on clinical needs.

目前6种间变性淋巴瘤激酶（ALK）抑制剂（包括克唑替尼、阿来替尼、塞瑞替尼、布格替尼、恩沙替尼和洛拉替尼）已获批用于ALK阳性晚期非小细胞肺癌的一线治疗，但临床选择仍面临挑战。

通过安全性、有效性、药学特性、经济性和其他属性5个维度综合评价6种ALK抑制剂，为临床用药决策提供循证依据。

资料来源于药品说明书、美国国立综合癌症网络（NCCN）、中国临床肿瘤学会（CSCO）及欧洲肿瘤内科学会（ESMO）指南、网状Meta分析，以及浙江省两定机构医疗保障信息平台、国家医保信息数据库、国家药品监督管理局药品审评中心等权威平台关于药品疗效、安全性、药品价格等评价所需数据。基于《中国医疗机构药品评价与遴选快速指南（第二版）》，采用德尔菲法构建包含安全性、有效性、药学特性、经济性和其他属性5个维度的综合评价体系对克唑替尼、阿来替尼、塞瑞替尼、布格替尼、恩沙替尼和洛拉替尼6种ALK抑制剂进行全面评估。由具备高级职称且在相关领域工作5年以上9人组成专家团队进行6轮讨论确定评价细则（3轮讨论确定评价条目，另3轮讨论确定各条目的分值分配），最终结果经2人小组根据建立的评价标准对6种ALK抑制剂进行独立评价和统计。

6种ALK抑制剂的综合评价排名为：布格替尼（85.5分）>阿来替尼（82.7分）>洛拉替尼（82.2分）>恩沙替尼（78.8分）>塞瑞替尼（77.4分）>克唑替尼（76.5分）。核心维度（安全性+有效性+药学特性）最优为阿来替尼（71.0分）。代际趋势评价结果显示：第二代>第三代>第一代（塞瑞替尼、恩沙替尼除外）；核心维度代际趋势评价结果显示：第三代>第二代>第一代（阿来替尼、塞瑞替尼除外）。

本研究证实不同ALK抑制剂在有效性、安全性、药学特性、经济性和其他属性5个维度各具优势，综合评分布格替尼高于其他ALK抑制剂，核心维度评分阿来替尼高于其他ALK抑制剂。第二代和第三代药物整体表现较好，这些评价结果可为医疗机构根据临床需求选择个体化治疗方案提供重要参考。