晚期非小細胞肺癌患者使用表皮生長因子受體酪氨酸激酶抑製劑與心血管疾病風險的關係

Abstract

背景 關於表皮生長因子受體酪氨酸激酶抑製劑（EGFR-TKI）與心血管疾病風險之間的關係仍然不明。本研究旨在評估臺灣晚期非小細胞肺癌患者接受EGFR-TKI治療後的心血管事件。 方法 本研究納入2011年至2016年期間接受EGFR-TKI或化學治療（化療）的新診斷晚期非小細胞肺癌患者，並追蹤至2018年。資料來自台灣癌症登記長表資料庫及全民健康保險研究資料庫。主要探討的心血管事件為冠狀動脈疾病，使用住院診斷碼、手術處置碼及死因定義。其他原因導致的死亡被視為競爭風險。利用Cox迴歸模型獲得多變項調整之特定原因的風險比率及其95%信賴區間比較接受EGFR-TKI（n= 15205；EGFR-TKI世代）和接受化療（n= 10614；化療世代）的患者發生冠狀動脈疾病的風險。 結果 在中位數為0.7年的追蹤期間，25,819位晚期非小細胞肺癌患者共發生397起冠狀動脈疾病。冠狀動脈疾病的發病率在EGFR-TKI世代為每千人年10.0例，在化療世代為每千人年19.1例。與接受化療的患者相比，接受 EGFR-TKI 的患者調整後的冠狀動脈疾病風險比率為0.65；95%信賴區間為0.52至0.81。心臟保護的效果在男性和非吸煙者中更為明顯。 結論 與化療相比，晚期非小細胞肺癌患者接受EGFR-TKI可降低心血管疾病的風險。尚須進一步的研究探討EGFR在心血管系統中的作用。

Introduction Evidence regarding the relationship between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and the risk of cardiovascular disease (CVD) is limited. This study aimed to evaluate the incident cardiovascular outcomes of patients with advanced non-small-cell lung cancer (NSCLC) treated with EGFR-TKIs in Taiwan. Methods Patients with newly diagnosed advanced NSCLC who received EGFR-TKI or chemotherapy between 2011 and 2016 were enrolled and followed up until 2018. Data were extracted from administrative databases. The primary outcome of interest was coronary artery disease (CAD). Death from other causes was considered a competing risk. We compared the risk of incident CAD between participants receiving EGFR-TKI (n= 15205; EGFR-TKI cohort) and chemotherapy (n= 10614; chemotherapy cohort) using multivariable-adjusted cause-specific hazard ratios (cause-specific HR) with 95% confidence intervals (CI) obtained from Cox’s regression model. Results A total of 397 CAD events occurred in 25,819 participants with advanced NSCLC during a median follow-up of 0.7 years. The incidence rates of CAD were 10.0 cases per 1,000 person-years in the EGFR-TKI cohort and 19.1 cases per 1,000 person-years in the chemotherapy cohort. The adjusted cause-specific HR of CAD in those who received EGFR-TKI was 0.65 (95% CI, 0.52-0.81), compared with those who received chemotherapy. The cardioprotective effect was more pronounced in men and non-smokers. Conclusion EGFR-TKI may reduce the risk of CVDs in patients with advanced NSCLC compared with chemotherapy. Further investigations on the EGFR-specific mechanisms related to the cardiovascular system are warranted.