目前有數種治療非小細胞肺癌的方式，傳統化學療法已經不再是唯一選擇。酪氨酸激酶抑制劑能結合在表皮生長因子受體，用來治療非小細胞肺癌。隨著標靶藥物 推陳出新有更多藥物可供我們選擇。目前衛生福利部已核可上市的肺癌標靶藥物共 有五種。第一代 gefitinib、erlotinib 屬可逆性抑制劑。第二代 afatinib、dacomitinib 作用機轉是與表皮生長因子受體形成不可逆的共價鍵，和第一代相比可以更廣泛地 阻斷 ErbB 家族 (erythroblastic leukemia viral oncogene homolog)，可惜亦會抑制正 常的 epithelial growth factor receptors，進而導致較嚴重副作用，在臨床使用上更應 留意副作用的發生。60~80% 患者服用第一代或第二代 tyrosine kinase inhibitor 可能 產生表皮生長因子受體突變，造成第 790 個胺基酸由蘇胺酸突變成甲硫胺酸，簡稱 T790M 突變 (p.Thr790Met point mutation)，第三代 osimertinib 對 T790M 突變之表 皮生長因子受體親合力更強，能選擇性抑制具有表皮生長因子受體突變，其嚴重不良 反應也比較少。此外 osimertinib 能穿透血腦障蔽，相較於其他藥品，osimertinib 能 進入腦中的比例較高，在中樞系統產生抗癌作用，對於產生腦轉移的患者是一大利 器。如何在臨床用藥上取得有效性與安全性之平衡，並替病人爭取更多的生存時間及維持良好的生活品質，是治療非小細胞肺癌很重要的課題。此篇目的將利用文獻回顧 的方式，討論不同酪氨酸激酶抑制劑的差異以及目前治療的新趨勢。

 

Traditional chemotherapy no longer remains the only option to treat non-smallcell lung cancer (NSCLC). Owing to their ability to bind with epithelial growth factor receptors (EGFRs), tyrosine kinase inhibitors (TKIs) can be used to treat NSCLC. The development of targeted drugs has increased the choice of medications. Five targeted therapy drugs for lung cancer have been approved by the Ministry of Health and Welfare, Taiwan. Gefitinib and erlotinib, first-generation drugs, are reversible TKIs. The second-generation drugs, afatinib and dacomitinib, form irreversible covalent bonds with EGFRs. Compared with the first-generation drugs, the second-generation drugs can more widely block the erythroblastic leukemia viral oncogene homolog (ErbB) protein family. However, they also inhibit normal EGFR functions, leading to severe issues, which warrant attention. Moreover, 60%–80% of patients taking firstgeneration or second-generation TKI drugs may have an EGFR mutation in which the 790th amino acid threonine is replaced by methionine; this point mutation is called p.Thr790Met (T790M). However, osimertinib has a stronger affinity for T790M and can selectively inhibit the EGFR mutation, with rare serious adverse reactions. Moreover, osimertinib can penetrate the blood–brain barrier. Osimertinib can enter the brain at a higher rate than other drugs and exert an anticancer effect in the central system. It is an excellent weapon against brain metastases. Achieving a balance between efficacy and safety in clinical medication, prolonging survival, and improving the quality-oflife are critical in NSCLC treatments. The purpose of this review article is to discuss the differences in TKIs and new trends in current NSCLC treatments.

 

Summited for publication: 2021.4.16; Accepted for publication: 2021.11.29