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.

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简报：免疫检查点抑制剂在 KRAS 突变型非小细胞肺癌 (NSCLC) 中的疗效

引言 KRAS 突变是晚期 NSCLC 中最常见的分子改变；如果没有可用的靶向治疗，它与预后不良有关。最近，免疫检查点抑制剂 (ICIs) 的开发丰富了 NSCLC 的治疗选择，关于其在 KRAS 突变 NSCLC 患者中的疗效数据不一致。本研究评估了 ICI 在晚期 KRAS 突变 NSCLC 中的常规疗效。方法 在这项回顾性研究中，从 2013 年 4 月至 2017 年 6 月期间接受 ICI 和可用分子分析的晚期 NSCLC 患者的医疗记录中提取临床数据。如果可利用，则进行程序性死亡配体 1 (PD-L1) 表达分析肿瘤材料可用。结果 共 282 名接受 ICI 治疗的（一线或以上）晚期 NSCLC（所有组织学亚组）患者接受 ICI（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 种（57.4%）具有 KRAS 突变，27 种（9.6%）具有其他突变，以及 93 种（33%）具有野生型表型。128 名患者 (45.4%) 可进行 PD-L1 分析，其中 45.3% 和 19.5% 的 PD-L1 表达分别为 1% 或更高和 50%（在病例中分别为 49.5% 和 21.2%） 85 名 KRAS 突变的 NSCLC 患者）。KRAS 突变 NSCLC 与其他 NSCLC 在客观缓解率、无进展生存期或总生存期方面没有显着差异。在主要 KRAS 突变亚型（G12A、G12C、G12D、G12V 和 G13C）之间未观察到总生存期或无进展生存期的显着差异。在 KRAS 突变的 NSCLC 中，与非 KRAS 突变的 NSCLC 不同，ICI 的疗效始终高于 PD-L1 在 1% 或更多肿瘤细胞中表达的患者，尽管没有统计学意义L1 在不到 1% 的肿瘤细胞中表达，当 PD-L1 表达高（PD-L1 表达≥50%）时，这一发现尤其正确。结论 对于 KRAS 突变型 NSCLC（所有突变亚型）患者，ICI 的疗效与其他类型 NSCLC 患者相似。与其他类型的 NSCLC 相比，PD-L1 表达似乎更能预测 ICI 在 KRAS 突变型 NSCLC 中的疗效。