晚期NSCLC EGFR-TKIs治疗失败应用PD-1/PD-L1抑制剂进展

Research progress of PD-1/PD-L1 inhibitors in advanced NSCLC patients after failure of EGFR-TKIs therapy

目的探讨程序性死亡受体-1/程序性死亡受体配体-1(PD-1/PD-L1)抑制剂在表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗失败的非小细胞肺癌(NSCLC)患者中的最佳治疗方案,为临床治疗提供参考。方法使用PubMed及中国知网数据库检索系统,以“非小细胞肺癌、EGFR-TKIs耐药、PD-1/PD-L1抑制剂”为中文关键词,“non-small cell lung cancer、EGFR-TKIs resistance、PD-1/PD-L1 inhibitors”为英文关键词,检索2009-09-03-2022-06-02相关文献。纳入标准:PD-1/PD-L1抑制剂用于EGFR-TKIs治疗失败的晚期NSCLC患者的相关研究。排除标准:数据陈旧的相关研究。共纳入文献56篇。结果PD-1/PD-L1抑制剂单药效果有限,联合EGFR-TKIs由于毒副作用大多停止用药,联合TGF-β及CTLA-4抑制剂或抗血管生成药物研究样本量有限,联合化疗或联合化疗及抗血管生成初见疗效,但联合方案的最优选择仍然存在争议。结论PD-1/PD-L1抑制剂在EGFR-TKIs治疗失败的晚期NSCLC患者的治疗中取得了一定的疗效,但如何根据不同的患者选择最优联合方案仍需要进一步探讨。

Objective To explore the best treatment plan of programmed death receptor-1/programmed death receptor-ligand 1(PD-1/PD-L1)inhibitors in non-small cell lung cancer(NSCLC)patients with failure of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)treatment and provide reference for clinical treatment.Methods The"non-small cell lung cancer,EGFR-TKIs resistance and PD-1/PD-L1 inhibitors"were selected as the key words from PubMed and Chinese National Knowledge Infrastructure databases.Relevant literatures were systematically searched from 2009-09-03 to 2022-06-02.Inclusion criteria were PD-1/PD-L1 inhibitors for advanced NSCLC patients who failed EGFR-TKIs treatment.Exclusion criteria were relevant studies with outdated data.A total of 56 articles were included.Results The efficacy of PD-1/PD-L1 inhibitor monotherapy was limited and the regimen to combine PD-1/PD-L1 inhibitors with EGFR-TKIs was mostly suspended due to severe toxic side effects.The sample size of PD-1/PD-L1 inhibitors combining with transforming growth factor-β(TGF-β)and cytotoxic T lymphocyte-associated antigen-4(CTLA-4)inhibitors or anti-angiogenic agents was limited.PD-1/PDL1 inhibitors combining with chemotherapy or combined with chemotherapy and anti-angiogenic agents have shown initial efficacy,but the optimal choice of combination projects is stil controversial.Conclusions PD-1/PD-L1 inhibitors have achieved certain efficacy in the treatment of advanced NSCLC patients with failure of EGFR-TKIs.However,further research still focuses on selecting the optimal combination regimen according to different patients.