Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Internal Medicine, Saitama Municipal Hospital, Saitama, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Lung Cancer. 2018 Oct;124:179-188. doi: 10.1016/j.lungcan.2018.08.012. Epub 2018 Aug 13.
Nivolumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, has been shown to yield a durable response and significant prolongation of the survival in some patients with non-small-cell lung cancer (NSCLC). However, identification of patients who are likely to respond to nivolumab remains difficult at present.
We conducted a retrospective analysis of the clinical data of 87 consecutive patients with advanced NSCLC seen in clinical practice who received nivolumab monotherapy at the National Cancer Center Hospital in Japan between January 2016 and July 2016 (discovery cohort). In addition, we also collected the clinical data of 75 patients who were administered nivolumab monotherapy between August 2016 and March 2017 (validation cohort). For this study, we focused on the changes in the lymphocyte-to-monocyte ratio (LMR) observed after nivolumab monotherapy.
In the discovery cohort, increase (≥10%) of the LMR at 4 weeks after the start of nivolumab monotherapy relative to the pretreatment LMR was positively correlated with an objective response (objective response rate (ORR); 39.4% vs 11.8%, p = 0.0065). When this cutoff value of ≥10% was used, increase of the LMR was significantly associated with a prolonged progression-free survival (PFS) (median PFS [mPFS]; 7.3 months vs 2.5 months, p = 0.0049) and overall survival (OS) (median survival time; 15.6 months vs 8.9 months, p = 0.014). In the validation cohort also, increase of the LMR was significantly associated with higher ORR (50.0% vs 20.0%, p = 0.015) and prolonged PFS (mPFS; not reached vs 3.1 months, p = 0.0092). On the other hand, no such correlation was observed among patients treated with docetaxel.
A rapid increase of the LMR was significantly associated with the effects of nivolumab monotherapy in our study cohort. Therefore, early change of the LMR may be used as a novel effective surrogate marker to decide on continuation of anti-PD-1 therapy.
纳武利尤单抗是一种抗程序性细胞死亡蛋白 1（PD-1）的单克隆抗体，已被证明在一些非小细胞肺癌（NSCLC）患者中能够产生持久的反应，并显著延长生存期。然而，目前仍然难以确定哪些患者可能对纳武利尤单抗有反应。
我们对 2016 年 1 月至 2016 年 7 月期间在日本国家癌症中心医院接受纳武利尤单抗单药治疗的 87 例晚期 NSCLC 患者的临床数据进行了回顾性分析（发现队列）。此外，我们还收集了 2016 年 8 月至 2017 年 3 月期间接受纳武利尤单抗单药治疗的 75 例患者的临床数据（验证队列）。在这项研究中，我们重点关注纳武利尤单抗单药治疗后 4 周淋巴细胞与单核细胞比值（LMR）的变化。
在发现队列中，与治疗前 LMR 相比，纳武利尤单抗单药治疗后 4 周 LMR 的升高（≥10%）与客观缓解率（ORR；39.4% vs 11.8%，p=0.0065）呈正相关。当使用≥10%这个截断值时，LMR 的升高与无进展生存期（PFS）的延长显著相关（中位 PFS[mPFS]；7.3 个月 vs 2.5 个月，p=0.0049）和总生存期（OS）（中位生存时间；15.6 个月 vs 8.9 个月，p=0.014）。在验证队列中，LMR 的升高也与更高的 ORR（50.0% vs 20.0%，p=0.015）和 PFS 的延长显著相关（mPFS；未达到 vs 3.1 个月，p=0.0092）。另一方面，在接受多西他赛治疗的患者中则没有观察到这种相关性。
在本研究队列中，LMR 的快速升高与纳武利尤单抗单药治疗的效果显著相关。因此，LMR 的早期变化可以作为一种新的有效的替代标志物，用于决定是否继续进行抗 PD-1 治疗。
