Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC)
Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC)
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DOI：
10.1016/j.jtho.2019.01.011
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发表时间：
2019-06-01
影响因子：
20.4
通讯作者：
Mascaux, Celine
中科院分区：
文献类型：
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作者：
Jeanson, Arnaud;Tomasini, Pascale;Mascaux, Celine
简介：KRAS突变是晚期NSCLC中发现的最常见的分子改变;它与无可用靶向治疗的不良预后相关。最近，免疫检查点抑制剂（ICI）的开发丰富了NSCLC的治疗选择，但关于其在KRAS突变型NSCLC患者中疗效的数据并不一致。本研究评估了ICI对晚期KRAS突变型非小细胞肺癌的常规疗效。方法：在这项回顾性研究中，临床数据提取自2013年4月至2017年6月期间接受ICI治疗的晚期非小细胞肺癌患者的病历，并进行了可用的分子分析。如果可利用的肿瘤材料可用，则进行程序性死亡配体1（PD-L1）表达的分析。共282例ICI治疗患者（一线或以上）晚期NSCLC（所有组织学亚组）（抗程序性死亡1、抗PD-L1或抗细胞毒性T淋巴细胞相关蛋白4抗体），包括162例KRAS突变27例（57.4%），其他突变27例（9.6%），野生型93例（33%）。PD-L1分析可用于128例患者（45.4%），其中45.3%和19.5%的PD-L1表达分别为1%或以上和50%（85例KRAS突变型NSCLC患者中分别为49.5%和21.2%）。KRAS突变型NSCLC与其他NSCLC之间的客观缓解率、无进展生存期或总生存期无显著差异。在主要KRAS突变亚型（G12 A、G12 C、G12 D、G12 V和G13 C）之间未观察到总生存期或无进展生存期的显著差异。与非KRAS突变型NSCLC不同，在KRAS突变型NSCLC中，与PD-L1表达低于1%的肿瘤细胞的患者相比，PD-L1表达≥ 1%的患者的ICI疗效始终更高，即使不具有统计学显著性，当PD-L1表达较高时，这一发现尤其如此结论：对于KRAS突变型NSCLC患者（所有突变亚型），ICI的疗效与其他类型NSCLC患者相似。PD-L1表达似乎与预测KRAS突变型NSCLC中ICI疗效的相关性高于其他类型的NSCLC。(C)2019年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: KRAS mutation is the most frequent molecular alteration found in advanced NSCLC; it is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC.Methods: In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and with available molecular analysis between April 2013 and June 2017. Analysis of programmed death ligand 1 (PD-L1) expression was performed if exploitable tumor material was available.Results: A total of 282 patients with ICI-treated (in the first line or more) advanced NSCLC (all histological subgroups) who were treated with ICIs (anti-programmed death 1, anti-PD-L1, or anti-cytotoxic T-lymphocyte associated protein 4 antibodies), including 162 (57.4%) with KRAS mutation, 27 (9.6%) with other mutations, and 93 (33%) with a wild-type phenotype, were identified. PD-L1 analysis was available for 128 patients (45.4%), of whom 45.3% and 19.5% had PD-L1 expression of 1% or more and 50%, respectively (49.5% and 21.2%, respectively, in the case of the 85 patients with KRAS-mutant NSCLC). No significant difference was seen in terms of objective response rates, progression-free survival, or overall survival between KRAS-mutant NSCLC and other NSCLC. No significant differences in overall survival or progression-free survival were observed between the major KRAS mutation subtypes (G12A, G12C, G12D, G12V, and G13C). In KRAS-mutant NSCLC, unlike in non-KRAS-mutant NSCLC, the efficacy of ICIs is consistently higher, even though not statistically significant, for patients with PD-L1 expression in 1% or more of tumor cells than for those with PD-L1 expression in less than 1% of tumor cells, and this finding is especially true when PD-L1 expression is high (PD-L1 expression >= 50%).Conclusion: For patients with KRAS-mutant NSCLC (all mutational subtypes), the efficacy of ICI is similar to that for patients with other types of NSCLC. PD-L1 expression seems to be more relevant for predicting the efficacy of ICIs in KRAS-mutant NSCLC than it is in other types of NSCLC. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.