First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Japan Red Cross Society, Nagano Red Cross Hospital, Nagano, Japan.
Thorac Cancer. 2021 Mar;12(5):603-612. doi: 10.1111/1759-7714.13788. Epub 2021 Jan 12.
Nivolumab is a second-line chemotherapy for non-small cell lung cancer (NSCLC). This study explored the impact of clinical biomarkers such as neutrophil:lymphocyte ratio (NLR), C-reactive protein:albumin ratio (CAR), and modified Glasgow prognostic score on the efficacy and outcome of nivolumab monotherapy in previously treated NSCLC patients.
We retrospectively analyzed advanced or postoperative recurrence of NSCLC in 113 patients in two Japanese facilities from January 2015 to December 2019. Optimal cutoff values of NLR and CAR were assessed by the area under the receiver operating characteristic curves predicting death events to conduct regression analysis. Baseline values and values collected eight weeks after nivolumab treatment were measured to investigate time-series changes of these markers.
The patients showed median overall survival (OS) and progression-free survival (PFS) of 14.0 months and 2.3 months, respectively, with both being significantly longer in patients with partial response (PR) than in patients with progressive disease (PD). Optimal cutoff levels for NLR and CAR were 5.8 and 0.83, with significant decrease in CAR (P = 0.002) from baseline levels in PR patients and significant increase in PD patients. Baseline CAR ≥0.83 was significantly associated with one-year mortality events and overall survival (OS), and multivariate analysis showed significant association of age ≤70 years, an Eastern Cooperative Oncology Group performance status score of 2 or 3, and a baseline CAR ≥0.83 with inferior OS.
For second-line nivolumab therapy, evaluation of baseline CAR and subsequent changes in CAR may be predictive of therapeutic response to nivolumab and long-term survival in NSCLC patients.
Significant findings of the study The baseline value of C-reactive protein:albumin ratio was significantly associated with one-year mortality and overall survival in non-small cell lung cancer patients treated with nivolumab. What this study adds Time-series change of C-reactive protein:albumin ratio may be useful for predicting the treatment efficacy in patients treated with nivolumab.
纳武利尤单抗是二线化疗药物,适用于非小细胞肺癌(NSCLC)。本研究探讨了中性粒细胞与淋巴细胞比值(NLR)、C 反应蛋白与白蛋白比值(CAR)和改良格拉斯哥预后评分等临床生物标志物对既往接受过治疗的 NSCLC 患者使用纳武利尤单抗单药治疗的疗效和结局的影响。
我们对 2015 年 1 月至 2019 年 12 月在日本的 2 家机构接受治疗的 NSCLC 晚期或术后复发的 113 例患者进行了回顾性分析。通过接受者操作特征曲线下面积评估 NLR 和 CAR 的最佳截断值,以预测死亡事件,并进行回归分析。测量纳武利尤单抗治疗 8 周后的基线值和治疗后 8 周的值,以研究这些标志物的时间序列变化。
患者的中位总生存期(OS)和无进展生存期(PFS)分别为 14.0 个月和 2.3 个月,部分缓解(PR)患者的 OS 和 PFS 均明显长于疾病进展(PD)患者。NLR 和 CAR 的最佳截断值分别为 5.8 和 0.83,PR 患者的 CAR 从基线水平显著下降(P = 0.002),PD 患者的 CAR 显著升高。基线 CAR≥0.83 与 1 年死亡率事件和总生存(OS)显著相关,多变量分析显示,年龄≤70 岁、东部肿瘤协作组体能状态评分 2 或 3 分和基线 CAR≥0.83 与 OS 不良显著相关。
对于二线纳武利尤单抗治疗,CAR 的基线值和随后的 CAR 变化评估可能有助于预测纳武利尤单抗治疗的疗效和 NSCLC 患者的长期生存。
本研究的重要发现:非小细胞肺癌患者接受纳武利尤单抗治疗后,C 反应蛋白与白蛋白比值的基线值与 1 年死亡率和总生存率显著相关。本研究的新发现:C 反应蛋白与白蛋白比值的时间序列变化可能有助于预测接受纳武利尤单抗治疗的患者的治疗效果。