針對早期非小細胞肺癌患者使用酪胺酸激酶抑制劑作為術後輔助療法療效之統合分析

Efficacy of EGFR-TKI as adjuvant therapy for resected non-small cell lung cancer (NSCLC): systematic review and meta-analysis

吳淑榕(Shu-Jung Wu)

指導教授 ： 余忠仁

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202103587

摘要

目的：診斷為早期非小細胞肺癌患者，在接受過手術完全切除後，對於輔助療法的選擇—表皮生長因子受體酪氨酸激酶抑製劑（EGFR-TKI）或者化學治療，目前尚未明確。EGFR-TKI在晚期帶有EGFR基因突變的非小細胞肺癌患者的療效中表現卓越，並在多個隨機對照臨床試驗(RCT)中，證實無疾病存活率(DFS)的改善。
研究方法：透過本文的統合分析，主要探討EGFR-TKI與化療或安慰劑用在做過完全手術切除且帶有EGFR基因突變的非小細胞肺癌患者的存活率效益。作者使用非小細胞肺癌、輔助療法及表皮生長因子受體酪氨酸激酶抑製劑做為關鍵字，透過Pubmed、Embase和Cochrane資料庫中進行文獻檢索，篩選自過去十年間發表的第二到三期臨床試驗，針對EGFR-TKI與化療或安慰劑直接比較，用在做過完全手術切除且帶有EGFR基因突變的非小細胞肺癌患者，一共納入五個符合條件的隨機對照試驗，接著使用RevMan 5.3版進行統合分析。
結論：使用EGFR-TKI作為輔助療法，其DFS (pooled HR: 0.37; CI: 0.21-0.64, I2: 87%)優於化療(HR: 0.48, 95% CI: 0.36-0.65)和安慰劑(HR: 0.34, 95% CI: 0.12-1.03)。此外，在次族群分析中也發現使用EGFR-TKI作為輔助療法對於帶有Exon 19 del或Exon 21 del基因突變的患者，其DFS都有良好的表現，HR:0.24 (95% CI:0.08-0.69); HR:0.43 (95% CI:0.26-0.71)。由於多數臨床試驗的總存活率尚未有完整的分析資料，因此總存活率在本次統合分析中未觀察到統計顯著差異(4 studies, pooled HR:0.89 95%; CI:0.65-1.24)。

關鍵字

非小細胞肺癌 ； 輔助療法 ； 表皮生長因子受體酪氨酸激酶抑製劑 ； 無疾病存活期 ； 表皮生長因子受體 ； 酪氨酸激酶抑製劑

並列摘要

The treatment choice of adjuvant therapy between Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) or chemotherapy after completed resection in early-stage NSCLC patients is not well-defined. EGFR-TKI has demonstrate an astonishing efficacy in EGFR sensitizing advanced NSCLC patients, and improved the DFS in several randomized control trials (RCTs). We performed this meta-analysis to conclude the survival benefit compares EGFR-TKI with chemotherapy or placebo in EGFR sensitizing NSCLC patients who received completed resection from phase III RCTs for the last ten years. A literature search of Pubmed, Embase and Cochrane was performed using relevant keywords of lung cancer and adjuvant and EGFR-TKI, five eligible RCTs were included, and performed by RevMan version 5.3. In conclusion, EGFR-TKIs group performed better DFS (pooled HR:0.37; CI:0.21-0.64, I2:87%) than chemotherapy (HR:0.48, 95% CI:0.36-0.65) and placebo (HR:0.34, 95% CI:0.12-1.03). Also, greater DFS had been seen in EGFR-TKIs group for Exon 19 del than Exon 21 del in the subgroup analysis, HR:0.24 (95% CI:0.08-0.69); HR:0.43 (95% CI:0.26-0.71), respectively. No statistically significance was found in overall survival due to the immature data (4 studies, pooled HR:0.89 95%; CI:0.65-1.24).

並列關鍵字

NSCLC ； resected non-small cell lung cancer ； EGFR-TKI ； adjuvant therapy ； DFS

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