一项评估 PD-L1 高 KRAS 突变型一线免疫检查点抑制剂治疗的晚期非小细胞肺癌（NSCLC）患者结局的单机构研究。

A single institution study evaluating outcomes of PD-L1 high KRAS-mutant advanced non-small cell lung cancer (NSCLC) patients treated with first line immune checkpoint inhibitors.

机构信息

Cancer Centre of Southeastern Ontario, Canada; Kingston Health Sciences Centre, Canada; Department of Medical Oncology, Queen's University, Canada.

Kingston Health Sciences Centre, Canada; Department of Pathology and Molecular Medicine, Queen's University, Canada.

出版信息

Cancer Treat Res Commun. 2021;27:100330. doi: 10.1016/j.ctarc.2021.100330. Epub 2021 Feb 6.

DOI:10.1016/j.ctarc.2021.100330

PMID:33581492

Abstract

AIM

This study aimed to evaluate the impact of KRAS status on the efficacy of first-line immune checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS

Patients with advanced incurable or metastatic NSCLC with PD-L1 ≥50% treated with palliative-intent, single-agent PD-1/PD-L1 inhibitors at the Cancer Centre of Southeastern Ontario were included. KRAS mutation status was determined via massively parallel sequencing. Primary study outcome was median overall survival (mOS).

RESULTS

Seventy-eight patients (59 non-squamous, 19 squamous) were identified; only non-squamous patients were included in KRAS mutation analyses. Thirty patients (51%) were KRAS-MT (mutant), with G12C (19%), G12V (15%), and G12D (13%) accounting for the most common KRAS mutation subtypes. There was no difference in mOS between KRAS-MT and KRAS-WT (wild-type) patients (12.9 vs. 19.3 months, p = 0.879). There was a non-significant trend towards worse mOS in KRAS G12C patients compared to non-G12C and KRAS-WT patients (11.4 vs. 44.9 vs. 19.3 months, p = 0.772). On multivariable analysis, KRAS-MT status was not associated with mOS (HR 0.901, 95%CI 0.417-1.946, p = 0.791). ECOG≥2 was an independent prognostic factor for worse mOS (HR 2.853, 95%CI 1.237-6.583, p = 0.014). Immune-related adverse events did not differ between KRAS-MT and KRAS-WT groups (48% vs. 52%, p = 1.000).

CONCLUSIONS

KRAS mutation status did not have a significant impact on ICI efficacy or safety. However, a non-significant trend towards worse survival was noted in patients treated with ICI whose tumours harboured the KRAS G12C variant. This study provides valuable information for comparative analysis in the future.

摘要

目的

本研究旨在评估 KRAS 状态对接受一线免疫检查点抑制剂（ICI）治疗的晚期非小细胞肺癌（NSCLC）患者疗效的影响。

患者和方法

纳入在安大略省东南部癌症中心接受姑息性单药 PD-1/PD-L1 抑制剂治疗的 PD-L1≥50%的晚期不可治愈或转移性 NSCLC 患者。通过大规模平行测序确定 KRAS 突变状态。主要研究结果为中位总生存期（mOS）。

结果

共纳入 78 例患者（59 例非鳞状，19 例鳞状）；仅对非鳞状患者进行 KRAS 突变分析。30 例患者（51%）为 KRAS-MT（突变），最常见的 KRAS 突变亚型为 G12C（19%）、G12V（15%）和 G12D（13%）。KRAS-MT 与 KRAS-WT（野生型）患者的 mOS 无差异（12.9 与 19.3 个月，p=0.879）。与非 G12C 和 KRAS-WT 患者相比，KRAS G12C 患者的 mOS 有下降的趋势，但无统计学意义（11.4 与 44.9 与 19.3 个月，p=0.772）。多变量分析显示，KRAS-MT 状态与 mOS 无关（HR 0.901，95%CI 0.417-1.946，p=0.791）。ECOG≥2 是 mOS 较差的独立预后因素（HR 2.853，95%CI 1.237-6.583，p=0.014）。KRAS-MT 与 KRAS-WT 组之间的免疫相关不良事件无差异（48%与 52%，p=1.000）。