Neutropenia, neutrophilia, and neutrophil–lymphocyte ratio as prognostic markers in patients with metastatic castration-resistant prostate cancer

Alexander Meisel*, Ronald de Wit, Stephane Oudard, Oliver Sartor, Frank Stenner-Liewen, Zhenming Shun, Meredith Foster, Ayse Ozatilgan, Mario Eisenberger, Johann S. de Bono

*Corresponding author for this work

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Abstract

Background and purpose: 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. Patients and methods: PROSELICA assessed the non-inferiority of cabazitaxel 20 mg/m2 (C20; n = 598) versus 25 mg/m2 (C25; n = 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. Results: PROSELICA confirmed the negative prognostic value of increased baseline NLR [⩾3, hazard ratio (HR) 1.40; p < 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 (n = 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 [n = 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)]. Conclusions: 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.

Original languageEnglish
JournalTherapeutic Advances in Medical Oncology
Volume14
Early online date1 Jun 2022
DOIs
Publication statusPublished - 2022

Bibliographical note

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: research and analysis were supported by Sanofi. The authors were responsible for all content and editorial decisions and received no honoraria for development of this manuscript. Editorial support was provided by Amber Wood of MediTech Media, funded by Sanofi.

Publisher Copyright:
© The Author(s), 2022.

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