Personalised Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–small-cell Lung Cancer: Consensus and Controversy

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ML Zhuo, J Wang

Hong Kong J Radiol 2010;13(Suppl):S10-5

The epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib and erlotinib, have been proven to provide significant benefit in progression-free survival and overall survival in patients who have received at least one line of prior chemotherapy. Subgroup analyses of previous placebo-controlled clinical trials demonstrated that epidermal growth factor receptor mutation–positive status was associated with improved outcomes with epidermal growth factor receptor tyrosine kinase inhibitor therapy, leading to further investigation of these agents in the first-line setting. However, selection by clinical characteristics has proved inadequate for identifying all patients with epidermal growth factor receptor mutation–positive disease. Recently, several randomised and multicentre phase III clinical trials investigated the efficacy and tolerability of first-line gefitinib or erlotinib versus standard chemotherapy regimens in patients with confirmed epidermal growth factor receptor– activating mutation non–small-cell lung cancer. The results demonstrated that epidermal growth factor receptor mutation is a key to achieving exceptional outcomes with tyrosine kinase inhibitor therapy, regardless of patient clinical characteristics. However, there are also some dilemmas in genotype-based personalised tyrosine kinase inhibitor treatment. It is not yet clear whether this approach should only be applied after standard first-line chemotherapy or be used as first-line therapy to start with. In addition, as a non-invasive and repeatable source of genotypic information, it is uncertain whether repeated determination of epidermal growth factor receptor mutation status in peripheral blood could be helpful. In future, more clinical studies combined with prospective molecular analysis are warranted to verify the best strategy for individualised target therapy in selected patients with non–small-cell lung cancer.





表皮生長因子受體(EGFR)酪胺酸激酶抑制劑(TKI)類藥物,包括gefitinib及erlotinib,已被證實 為至少已經接受一線化療的病人提高無惡化生存期及總生存時間。採用安慰劑對照的臨床研究的亞 組分析顯示,EGFR突變狀況與EGFR-TKI治療帶來的改善有關,令至有更多關於使用EGFR-TKI作 一線治療的研究。儘管如此,純粹用臨床特徵辨別所有具EGFR突變的病人並不足夠。最近有幾個 隨機及多中心III期臨床研究探討在確認有EGFR突變的非小細胞肺癌患者中,比較標準化療及使用gefitinib或erlotinib作為一線治療的療效與耐受性。結果顯示EGFR突變是TKI治療達至理想效果的一 個關鍵,與病人的臨床特徵無關。可是,以基因型為基礎的個體化TKI治療有些兩難局面。究竟這 種療法應該在標準一線治療後才施用,還是本身應作為一線治療的藥物,並未有清晰結論。並且作 為一種非創傷性及可重複性的基因型資訊,重複外周血液測試EGFR突變狀況未知是否真的有幫助。 以後需要有更多的包括分子分析的前瞻性臨床研究來驗證非小細胞肺癌患者的最佳個體化標靶治療。