Molecular Characteristics and Pretreatment Neutrophil-to-Lymphocyte Ratio as Predictors of Durable Clinical Benefit from Immune Checkpoint Inhibition in Non-Small Cell Lung Cancer

IF 3.3 3区 医学 Q2 ONCOLOGY
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Abstract

Background

Prior research in non-small cell lung cancer (NSCLC) has shown that tumors with specific driver mutations may be less likely to respond to immune checkpoint inhibitors (ICI). In this analysis, we evaluated the characteristics of patients with durable clinical benefit (DCB) to ICI compared to those with no durable clinical benefit (NDB), with emphasis on the role of molecular alterations in EGFR, ALK, and ROS1 and pretreatment neutrophil-to-lymphocyte ratio (NLR).

Methods

We retrospectively collected clinical characteristics and outcomes for patients who initiated ICI monotherapy for advanced NSCLC at Stanford University between April 2015 and May 2018. Patients were classified as having DCB if time on ICI therapy was greater than or equal to 180 days, or NDB if less than 180 days. Outcomes included best radiographic benefit while on ICI and survival from time of ICI initiation.

Results

Of 123 patients treated with ICI for NSCLC, 28 patients had DCB (23%), while 95 had NDB (77%). Median overall survival from initiation of ICI in the 33 patients with molecular alterations in EGFR (n = 31), ALK, or ROS1 and NLR of 5.9 or higher was 2.0 months, compared to 8.1 months in patients with these genomic alterations and NLR less than 5.9. Median overall survival in patients without alterations in EGFR, ALK, or ROS1 and NLR of 5.9 or higher was 4.3 months, compared to 12.1 months in patients with NLR less than 5.9 (P = .023).

Conclusions

Elevation in pretreatment NLR was associated with significantly lower overall median survival from initiation of ICI, particularly when in combination with NSCLC with alterations in EGFR, ALK, or ROS1. This finding could influence clinical practice as NLR is readily available through routine blood testing.

分子特征和治疗前中性粒细胞与淋巴细胞比率是非小细胞肺癌患者从免疫检查点抑制疗法中获得持久临床获益的预测因素
之前对非小细胞肺癌(NSCLC)的研究表明,具有特定驱动突变的肿瘤可能不太可能对免疫检查点抑制剂(ICI)产生反应。在这项分析中,我们评估了与无持久临床获益(NDB)的患者相比,对 ICI 有持久临床获益(DCB)的患者的特征,重点是分子改变和治疗前中性粒细胞与淋巴细胞比值(NLR)的作用。我们回顾性地收集了2015年4月至2018年5月期间斯坦福大学开始接受ICI单药治疗的晚期NSCLC患者的临床特征和预后。如果患者接受 ICI 治疗的时间大于或等于 180 天,则被归类为 DCB;如果小于 180 天,则被归类为 NDB。研究结果包括接受 ICI 治疗期间的最佳放射学疗效以及从开始接受 ICI 治疗时算起的存活率。在接受 ICI 治疗的 123 名 NSCLC 患者中,28 名患者接受了 DCB(23%)治疗,95 名患者接受了 NDB(77%)治疗。在33例发生Ⅳ或Ⅴ级分子改变且NLR大于或等于5.9的患者中,从开始接受ICI治疗起的中位总生存期为2.0个月,而发生这些基因组改变且NLR小于5.9的患者的中位总生存期为8.1个月。NLR为5.9或更高的患者的中位总生存期为4.3个月,而NLR低于5.9的患者的中位总生存期为12.1个月 ( = .023)。治疗前NLR升高与ICI起始总生存期中位数明显降低有关,尤其是与NSCLC中or发生改变的患者合并治疗时。
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来源期刊
Clinical lung cancer
Clinical lung cancer 医学-肿瘤学
CiteScore
7.00
自引率
2.80%
发文量
159
审稿时长
24 days
期刊介绍: Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.
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