Abstract

Background

Immunotherapy modified advanced lung cancer treatment. Unfortunately, not all patients respond to it and little is known about predictive markers of response. Recently, a lung immune prognostic index (LIPI) was developed to predict outcomes. Neutrophil-lymphocyte ratio (NLR) has also been shown as possible marker of response to immune checkpoint inhibitors. The aim of this study is to evaluate the prognostic value of both LIPI and NLR in patients with advanced lung cancer treated with anti-PD1 drugs, pembrolizumab and nivolumab.

Methods

Data from patients diagnosed with lung cancer (stage III-IV) treated with pembrolizumab and nivolumab, from a Portuguese tertiary cancer centre were reviewed retrospectively (July’15 to July’19). LIPI and NLR were calculated before the beginning of immune checkpoints inhibitors. NLR was calculated as the ratio between neutrophils and lymphocytes. NLR was categorized into low (≤ median NLR in our cohort) and high NLR (>median). LIPI score results from NLR and LDH level and has 3 different risk categories: low, intermediate and high. Univariate analysis and multivariable analysis (Cox model adjusted for age, EGFR status, PD-L1 expression and previous treatment) were done to evaluate the association between LIPI and NLR with time to progression (TTP) and overall survival (OS).

Results

In our cohort, 120 patients were treated, according to PD-L1 expression, with pembrolizumab (83) and nivolumab (37). Median follow-up in living patients was 13 months, having occurred 60 deaths and 54 disease progression. In both univariate (p = 0.019) and multivariable (p = 0.001) analysis, LIPI score was an independent prognostic factor for OS but not for TTP. HR for intermediate vs low LIPI score was 3.1 (95%CI 1.1-8.8) and HR for high vs low LIPI score was 7.5 (95% CI = 2.5-22.8). Similarly, in univariate (p = 0.007) and multivariable (p = 0.006) analysis, NLR was an independent prognostic factor for OS but not for TTP. HR for high NLR was 2.9 (95% CI = 1.3-6.4).

Conclusion

In our cohort of patients, both LIPI score and NLR are prognostic factors for overall survival in advanced lung cancer patients treated with pembrolizumab and nivolumab. Prospective studies are needed to validate the value of these biomarkers in immunotherapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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免疫疗法治疗的肺癌患者的21P预后生物标志物

抽象的

背景

免疫疗法改良了晚期肺癌的治疗。不幸的是，并非所有患者都对此有反应，对反应的预测指标知之甚少。最近，开发了一种肺免疫预后指数（LIPI）来预测结局。中性粒细胞-淋巴细胞比率（NLR）也已被证明是对免疫检查点抑制剂反应的可能标志物。这项研究的目的是评估LIPI和NLR在使用抗PD1药物，派姆单抗和nivolumab治疗的晚期肺癌患者中的预后价值。

方法

回顾性分析了葡萄牙三级癌症中心诊断为接受pembrolizumab和nivolumab治疗的肺癌（III-IV期）患者的数据（7月15日至19年7月）。LIPI和NLR是在免疫检查点抑制剂开始之前计算的。NLR计算为嗜中性粒细胞和淋巴细胞之间的比率。NLR分为低（在我们的队列中≤中值NLR）和高NLR（>中位数）。LIPI评分由NLR和LDH水平得出，具有3个不同的风险类别：低，中和高。进行了单变量分析和多变量分析（针对年龄，EGFR状态，PD-L1表达和先前治疗进行了校正的Cox模型）以评估LIPI和NLR与进展时间（TTP）和总生存期（OS）的关联。

结果

在我们的队列中，根据PD-L1表达，使用派姆单抗（83）和尼古拉单抗（37）治疗了120例患者。在役患者的中位随访时间为13个月，已发生60例死亡和54例疾病进展。在单变量（p = 0.019）和多变量（p = 0.001）分析中，LIPI评分是OS的独立预后因素，而对于TTP则不是。LIPI评分中级与低级的HR为3.1（95％CI 1.1-8.8），LIPI评分高级与低级的HR为7.5（95％CI = 2.5-22.8）。同样，在单变量（p = 0.007）和多变量（p = 0.006）分析中，NLR是OS而非TTP的独立预后因素。高NLR的HR为2.9（95％CI = 1.3-6.4）。

结论

在我们的患者队列中，LIPI评分和NLR均为接受pembrolizumab和nivolumab治疗的晚期肺癌患者总体生存的预后因素。需要进行前瞻性研究以验证这些生物标记物在免疫治疗中的价值。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

所有作者均声明没有利益冲突。