Neutrophil:Lymphocyte Ratio [NLR] in patients with mCRPC treated with Cabazitaxel v. Abiraterone or Enzalutamide in the CARD study

[pjoshea13]

New international study - 20 authors from 19 institutions - headed by Johann de Bono [1].

Here is an old post:

"Inflammation. [1] Neutrophil-to-Lymphocyte Ratio [NLR]" [2].

The NLR is a recurring topic here.

Basically, a high NLR - a sign of subclinical inflammation - is a mortality risk factor and has been associated with poorer outcome when starting various PCa treatments. The message is that the inflammation should be addressed ASAP.

But de Bono & de Wit have some good news.

"CARD was a multicenter, open-label study that randomized patients with {metastatic CRPC} mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day)."

"For cabazitaxel, there was no OS {overall survival} difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively ..).

"Patients receiving an ARTA {androgen-receptor-targeted agent } with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively ...)."

{"ARTA" is shorthand for abiraterone or enzalutamide - both target the AR axis.}

What is a high NLR in this study? "≥ median (3.38)"

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/344...

Full text: esmoopen.com/article/S2059-...

ESMO Open

. 2021 Aug 24;6(5):100241. doi: 10.1016/j.esmoop.2021.100241. Online ahead of print.

Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study

R de Wit 1 , C Wülfing 2 , D Castellano 3 , G Kramer 4 , J-C Eymard 5 , C N Sternberg 6 , K Fizazi 7 , B Tombal 8 , A Bamias 9 , J Carles 10 , R Iacovelli 11 , B Melichar 12 , Á Sverrisdóttir 13 , C Theodore 14 , S Feyerabend 15 , C Helissey 16 , M C Foster 17 , A Ozatilgan 17 , C Geffriaud-Ricouard 18 , J de Bono 19

Affiliations collapse

Affiliations

1 Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: [e-mail].

2 Department of Urology, Asklepios Tumorzentrum, Hamburg, Germany.

3 Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain.

4 Department of Urology, Medical University of Vienna, Vienna, Austria.

5 Department of Medical Oncology, Institute Jean Godinot, Reims, France.

6 Division of Hematology and Medical Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, USA.

7 Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France; University of Paris Saclay, Saint-Aubin, France.

8 Institut de Recherche Clinique, Université Catholique de Louvain, Louvain, Belgium.

9 Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.

10 Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.

11 Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy; Department of Medical Oncology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy.

12 Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.

13 Department of Oncology, Landspitali University Hospital, Reykjavik, Iceland.

14 Department of Oncology, Foch Hospital, Suresnes, France.

15 Studienpraxis Urologie, Nürtingen, Germany.

16 Hôpital d'Instruction des Armées Bégin, Saint Mandé, France.

17 Global Medical Oncology, Sanofi, Cambridge, USA.

18 Europe Medical Oncology, Sanofi, Paris, France.

19 Division of Clinical Studies, The Institute of Cancer Research, London, UK; Prostate Targeted Therapy Group, Royal Marsden Hospital, London, UK.

PMID: 34450475 DOI: 10.1016/j.esmoop.2021.100241

Abstract

Background: There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker.

Patients and methods: CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan-Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS.

Results: The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608).

Conclusions: High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.

Keywords: abiraterone; cabazitaxel; enzalutamide; metastatic castration-resistant prostate cancer; neutrophil-to-lymphocyte ratio; prognostic factor.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

***

[2] healthunlocked.com/advanced...

[J_Monacello]

Patrick, you say, "Basically, a high NLR - a sign of subclinical inflammation - is a mortality risk factor and has been associated with poorer outcome when starting various PCa treatments. The message is that the inflammation should be addressed ASAP." But what exactly can be done, what should be addressed? My understanding is that there is nothing that can be done to alter the NLR. Please advise. Thanks.

[pjoshea13 in reply to J_Monacello]

old post: healthunlocked.com/advanced...