Human epidermal growth factor receptor 2-tyrosine kinase inhibitors (HER2-TKIs) have been extensively utilized for treating HER2-positive metastatic breast cancer (MBC), with numerous clinical trial reports available. We aim to systematically perform a comprehensive clinical evaluation on HER2-TKIs, provide a reference for the clinical rational use of drugs, and serve for the decision-making of the national drug policy. We performed comprehensive clinical evaluation in six dimensions including safety, effectiveness, economy, suitability, accessibility, and innovation through meta-analysis, literature review, drug administration websites, and other relevant medication data to analyze HER2-TKIs in treating HER2-positive MBC. For safety, the risk of ≥ grade 3 adverse events among pyrotinib, lapatinib, and neratinib is not significantly different. Furthermore, pyrotinib and neratinib were found to be higher in the risk of ≥ grade 3 diarrhea than lapatinib, however the risk could be reversed and prevented with loperamide. Regarding effectiveness and economy, pyrotinib was confirmed to have the best efficacy and cost-utility value, neratinib the second, and lapatinib the third. As regards innovation and suitability, pyrotinib showed better than other HER2-TKIs. In addition, pyrotinib received a higher recommendation than other HER2-TKIs in patients with HER2-positive MBC. The accessibility of pyrotinib was found to be the best with better urban, rural, and national affordability and lower annual treatment costs. Pyrotinib is more valuable in clinics with better safety, effectiveness, economy, suitability, accessibility, and innovation in HER2-positive MBC. This study could provide references for the clinical application of HER2-TKIs in treating HER2-positive MBC.

中文翻译：

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对既往接受过治疗的 HER2 阳性转移性乳腺癌患者进行 HER2-TKIs 的综合临床评估。

人表皮生长因子受体2-酪氨酸激酶抑制剂（HER2-TKI）已广泛用于治疗HER2阳性转移性乳腺癌（MBC），并有大量临床试验报告。我们旨在系统地对HER2-TKIs进行全面的临床评价，为临床合理用药提供参考，为国家药物政策决策服务。我们通过荟萃分析、文献综述、药品管理网站和其他相关用药数据，从安全性、有效性、经济性、适用性、可及性和创新性等六个维度进行全面的临床评价，分析HER2-TKIs治疗HER2阳性MBC的效果。就安全性而言，吡咯替尼、拉帕替尼和来那替尼之间≥3级不良事件的风险没有显着差异。此外，发现吡咯替尼和来那替尼发生 3 级以上腹泻的风险高于拉帕替尼，但洛哌丁胺可以逆转和预防该风险。从有效性和经济性来看，吡咯替尼被证实具有最佳疗效和成本效用价值，来那替尼次之，拉帕替尼第三。在创新性和适用性方面，吡咯替尼表现出优于其他HER2-TKI。此外，在 HER2 阳性 MBC 患者中，吡咯替尼比其他 HER2-TKI 获得了更高的推荐。吡咯替尼的可及性被发现是最好的，城市、农村和全国的负担能力更好，年度治疗费用更低。吡咯替尼在 HER2 阳性 MBC 中具有更好的安全性、有效性、经济性、适用性、可及性和创新性，在临床上更有价值。该研究可为HER2-TKIs治疗HER2阳性MBC的临床应用提供参考。