EGFR突变型非小细胞肺癌EGFR-TKI获得性耐药后免疫治疗现状

doi:10.3760/cma.j.cn371439-20220719-00020

摘要/Abstract

摘要：

表皮生长因子受体（EGFR）突变型晚期非小细胞肺癌（NSCLC）既往被认为是一种免疫“冷肿瘤”。然而，最近研究显示EGFR-酪氨酸激酶抑制剂（TKI）治疗可使机体免疫状态从免疫抑制向免疫支持转化，这为免疫治疗带来了新的希望。EGFR突变型NSCLC在发生EGFR-TKI获得性耐药后的免疫治疗策略主要包括4种：单一免疫治疗（Im）、免疫治疗加化疗（Im+C）、免疫治疗加抗血管生成治疗（Im+A）、免疫治疗联合抗血管生成和化疗（Im+A+C）。其中，Im效果显著低于单一化疗，疗效极其有限；而Im+A临床研究很少，尚缺乏证据。Im+C与Im+A+C联合方案的效果显著优于单一化疗，而Im+A+C的疗效较Im+C有明显优势。此外，EGFR L858R突变亚群比EGFR 19del突变亚群从Im+C中获益更大，而T790M阴性亚组较T790M阳性亚组从Im+A+C中获益更大。总之，对于EGFR突变型NSCLC发生EGFR-TKI获得性耐药患者，免疫治疗联合化疗和抗血管生成治疗是一种新的有前景的治疗方法。

关键词: 癌, 非小细胞肺, 免疫治疗, 表皮生长因子受体, 酪氨酸激酶抑制剂

Abstract:

Epidermal growth factor receptor （EGFR）-mutant advanced non-small cell lung cancer （NSCLC） was previously regarded as a cold tumor according to tumor immune microenvironment （TIME）. However，recent studies have found that EGFR-tyrosine kinase inhibitors （EGFR-TKIs） treatment can transform the host immunity from immunosuppressive to immunosupportive state，bringing new hope for immunotherapy. There are four main therapeutic strategies for patients after EGFR-TKIs acquired resistance： immunotherapy alone （Im），immunotherapy plus chemotherapy （Im+C），immunotherapy plus antiangiogenic drugs （Im+A），and immunotherapy combined with antiangiogenic drugs and chemotherapy （Im+A+C）. Among them，the efficacy of Im is extremely limited，being significantly lower than that of chemotherapy alone，while there is still scarce evidence for the efficacy of Im+A with few clinical studies. The combination of Im+C and Im+A+C shows better efficacy than chemotherapy alone. Im+A+C has a superior clinical outcome to Im+C. Additionally，the EGFR L858R mutation subgroup benefits more from Im+C than the EGFR 19 del mutation subgroup. The T790M-negative subgroup has a greater benefit from Im+A+C than the T790M-positive subgroup. In general，the strategy of combining immunotherapy with chemotherapy and/or an antiangiogenic drug represents a novel and promising method for treating EGFR-mutant NSCLC after EGFR-TKI failure.

Key words: Carcinoma, non-small-cell lung, Immunotherapy, Epidermal growth factor receptors, Tyrosine kinase inhibitors

张碧霞, 丁江华. EGFR突变型非小细胞肺癌EGFR-TKI获得性耐药后免疫治疗现状[J]. 国际肿瘤学杂志, 2023, 50(2): 97-101.

Zhang Bixia, Ding Jianghua. Immunotherapy for EGFR-mutant non-small cell lung cancer after EGFR-TKI acquired resistance[J]. Journal of International Oncology, 2023, 50(2): 97-101.

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