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非小细胞肺癌中除……之外具有可操作突变的免疫疗法

Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than .

作者信息

Seegobin Karan, Majeed Umair, Wiest Nathaniel, Manochakian Rami, Lou Yanyan, Zhao Yujie

机构信息

Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, United States.

Department of Medicine, Mayo Clinic, Jacksonville, FL, United States.

出版信息

Front Oncol. 2021 Dec 1;11:750657. doi: 10.3389/fonc.2021.750657. eCollection 2021.

Abstract

While first line targeted therapies are the current standard of care treatment for non-small cell lung cancer (NSCLC) with actionable mutations, the cancer cells inevitably acquire resistance to these agents over time. Immune check-point inhibitors (ICIs) have improved the outcomes of metastatic NSCLC, however, its efficacy in those with targetable drivers is largely unknown. In this manuscript, we reviewed the published data on ICI therapies in NSCLC with , , , , , , , and alterations. We found that the objective response rates (ORRs) associated with ICI treatments in lung cancers harboring the (0-54%), (12-49%), and (18.7-66.7%) alterations were comparable to non-mutant NSCLC, whereas the ORRs in fusion NSCLC (less than10% in all studies but one) and fusion NSCLC (0%) were relatively low. The ORRs reported in small numbers of patients and studies of fusion, fusion, and mutant NSCLC were 0-17%, 50% and 7-23%, respectively, making the efficacy of ICIs in these groups of patients less clear. In most studies, no significant correlation between treatment outcome and PD-L1 expression or tumor mutation burden (TMB) was identified, and how to select patients with NSCLC harboring actionable mutations who will likely benefit from ICI treatment remains unknown.

摘要

虽然一线靶向治疗是目前针对具有可操作突变的非小细胞肺癌(NSCLC)的标准治疗方法,但随着时间的推移,癌细胞不可避免地会对这些药物产生耐药性。免疫检查点抑制剂(ICI)改善了转移性NSCLC的治疗效果,然而,其在具有可靶向驱动因素的患者中的疗效在很大程度上尚不清楚。在本手稿中,我们回顾了关于ICI治疗在具有 、 、 、 、 、 、 和 改变的NSCLC中的已发表数据。我们发现,在携带 (0 - 54%)、 (12 - 49%)和 (18.7 - 66.7%)改变的肺癌中,与ICI治疗相关的客观缓解率(ORR)与非突变NSCLC相当,而在 融合NSCLC(除一项研究外所有研究中均低于10%)和 融合NSCLC(0%)中的ORR相对较低。在少数关于 融合、 融合和 突变NSCLC患者及研究中报告的ORR分别为0 - 17%、50%和7 - 23%,这使得ICI在这些患者群体中的疗效不太明确。在大多数研究中,未发现治疗结果与PD - L1表达或肿瘤突变负荷(TMB)之间存在显著相关性,并且如何选择可能从ICI治疗中获益的具有可操作突变的NSCLC患者仍然未知。

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