Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
Eisai Co., Ltd., Koishikawa, Bunkyo-ku, Tokyo, Japan.
Breast Cancer. 2020 Jul;27(4):706-715. doi: 10.1007/s12282-020-01067-2. Epub 2020 Mar 5.
Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS).
The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively.
Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin.
This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures.
www.ClinicalTrials.gov code: NCT00388726.
埃博霉素是一种非紫杉烷类微管动力学合成抑制剂，广泛用于治疗局部晚期或转移性乳腺癌（MBC）。埃博霉素对肿瘤微环境具有免疫调节活性。基线中性粒细胞与淋巴细胞比值（NLR）是免疫状态的标志物，可能预测埃博霉素治疗的无进展生存期。本事后分析评估了总生存期（OS）的预测因素。
在 MBC 患者中进行的埃博霉素与医生选择的治疗（TPC）的开放标签 III 期研究（EMBRACE）提供了原始数据。基线绝对淋巴细胞计数（ALC）和 NLR 在 751 例和 713 例患者中是可评估的。
与 TPC 相比，基线 ALC≥1500/µl 的患者中，埃博霉素延长了 OS（风险比[HR]0.586；95%置信区间[CI]0.437-0.784；P<0.001）。对于 ALC<1500/µl 的患者，治疗之间无显著差异（HR 1.002；95%CI 0.800-1.253；P=0.989）。进行了单变量和多变量分析，并确定基线 ALC 是埃博霉素治疗患者 OS 的潜在预测因素。OS 的交互分析支持 1500/µl 作为潜在的差异截定点值。NLR 截断值为 3 时与 OS 延长相关（埃博霉素组）。然而，在 TPC 组中也观察到了类似的结果，没有明显的交互作用效应，这表明 NLR 可能是一种普遍的预后标志物，而不是埃博霉素 OS 的特定预测因子。
这项产生假说的研究推测，基线 ALC 可能是埃博霉素治疗的 MBC 患者更长 OS 的独立预测因素，并且可能具有临床影响，因为它可以在无需额外侵入性程序的情况下进行评估。
www.ClinicalTrials.gov 编号：NCT00388726。
