Meisel Alexander, de Wit Ronald, Oudard Stephane, Sartor Oliver, Stenner-Liewen Frank, Shun Zhenming, Foster Meredith, Ozatilgan Ayse, Eisenberger Mario, de Bono Johann S
Department of Nuclear Medicine Zurich, University Hospital of Zurich, Raemistr. 100, 8091 Zurich, Switzerland.
Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Ther Adv Med Oncol. 2022 Jun 1;14:17588359221100022. doi: 10.1177/17588359221100022. eCollection 2022.
Chemotherapy-induced neutropenia and neutrophil-to-lymphocyte ratio (NLR) are potentially useful prognostic markers in patients with metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis investigated whether these markers can be utilized for dose considerations and evaluated the prognostic impact of leukocyte subtypes.
PROSELICA assessed the non-inferiority of cabazitaxel 20 mg/m (C20; = 598) 25 mg/m (C25; = 602) for overall survival (OS) in patients with mCRPC previously treated with docetaxel. The association of grade ⩾ 3 neutropenia, NLR, baseline neutrophilia and lymphopenia with OS, progression-free survival (PFS), and prostate-specific antigen response rate (PSArr) was investigated by an unplanned uni- and multivariate analyses.
PROSELICA confirmed the negative prognostic value of increased baseline NLR [⩾3, hazard ratio (HR) 1.40; < 0.0001], but did not identify a subgroup of patients benefiting more from C20 or C25. In this post hoc analysis, patients who developed grade ⩾3 neutropenia ( = 673) had a significantly improved OS [∆OS = 2.7 months, HR = 0.78 (95% CI 0.68-0.89)] with the greatest advantage observed in patients with baseline neutrophilia [ = 85; 5.3 months, 0.60 (0.42-0.84)]. After adjustment for the Halabi criteria, neutropenia grade ⩾ 3 was the only biomarker that remained significantly associated with OS [ (HR 0.86 (0.75-0.98)], PFS [HR 0.78 (0.68-0.88)], and PSArr [odds ratio (OR) 1.82 (1.37-2.41)] while neutrophilia showed the strongest association with OS [1.53 (1.29-1.81)].
Grade ⩾ 3 neutropenia was the only leukocyte-based biomarker associated with all key outcome parameters in mCRPC patients receiving cabazitaxel and might be able to overcome the negative prognostic effect of baseline neutrophilia.
NCT01308580.
化疗引起的中性粒细胞减少和中性粒细胞与淋巴细胞比值（NLR）可能是转移性去势抵抗性前列腺癌（mCRPC）患者有用的预后标志物。这项事后分析研究了这些标志物是否可用于剂量考量，并评估了白细胞亚型的预后影响。
PROSELICA评估了卡巴他赛20mg/m²（C20；n = 598）与25mg/m²（C25；n = 602）对既往接受多西他赛治疗的mCRPC患者总生存期（OS）的非劣效性。通过计划外的单因素和多因素分析研究了≥3级中性粒细胞减少、NLR、基线中性粒细胞增多和淋巴细胞减少与OS、无进展生存期（PFS）及前列腺特异性抗原反应率（PSArr）之间的关联。
PROSELICA证实了基线NLR升高的负面预后价值[≥3，风险比（HR）1.40；P < 0.0001]，但未识别出从C20或C25中获益更多的患者亚组。在这项事后分析中，发生≥3级中性粒细胞减少的患者（n = 673）OS显著改善[OS差值 = 2.7个月，HR = 0.78（95%CI 0.68 - 0.89）]，在基线中性粒细胞增多的患者中优势最大[n = 85；5.3个月，HR = 0.60（0.42 - 0.84）]。在根据哈拉比标准进行调整后，≥3级中性粒细胞减少是唯一仍与OS显著相关的生物标志物[HR 0.86（0.75 - 0.98）]、PFS[HR 0.78（0.68 - 0.88）]及PSArr[优势比（OR）1.82（1.37 - 2.41）]，而中性粒细胞增多与OS的关联最强[HR 1.53（1.29 - 1.81）]。
≥3级中性粒细胞减少是接受卡巴他赛治疗的mCRPC患者中唯一与所有关键结局参数相关的基于白细胞的生物标志物，且可能能够克服基线中性粒细胞增多的负面预后影响。
NCT01308580。
