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.
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.
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).
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.
ESMO open. 2021 Aug 24 [Epub ahead of print]
R de Wit, C Wülfing, D Castellano, G Kramer, J-C Eymard, C N Sternberg, K Fizazi, B Tombal, A Bamias, J Carles, R Iacovelli, B Melichar, Á Sverrisdóttir, C Theodore, S Feyerabend, C Helissey, M C Foster, A Ozatilgan, C Geffriaud-Ricouard, J de Bono
Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: ., Department of Urology, Asklepios Tumorzentrum, Hamburg, Germany., Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain., Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Medical Oncology, Institute Jean Godinot, Reims, France., Division of Hematology and Medical Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, USA., Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France; University of Paris Saclay, Saint-Aubin, France., Institut de Recherche Clinique, Université Catholique de Louvain, Louvain, Belgium., Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy; Department of Medical Oncology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy., Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic., Department of Oncology, Landspitali University Hospital, Reykjavik, Iceland., Department of Oncology, Foch Hospital, Suresnes, France., Studienpraxis Urologie, Nürtingen, Germany., Hôpital d'Instruction des Armées Bégin, Saint Mandé, France., Global Medical Oncology, Sanofi, Cambridge, USA., Europe Medical Oncology, Sanofi, Paris, France., Division of Clinical Studies, The Institute of Cancer Research, London, UK; Prostate Targeted Therapy Group, Royal Marsden Hospital, London, UK.