ESMO Virtual Congress 2020: Neutrophil-Lymphocyte Ratio as a Prognostic and Predictive Biomarker in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Cabazitaxel vs. Abiraterone or Enzalutamide in the CARD Study

(UroToday.com) It is well known that inflammation is a hallmark of cancer, harboring a critical role in tumor development and metastatic progression in many cancers, including prostate cancer.1 It has been shown that baseline neutrophil-to-lymphocyte ratio (NLR), calculated by dividing the absolute peripheral neutrophil count by the absolute lymphocyte count, is an accessible and inexpensive marker of cancer inflammation.When this ratio is high at baseline, data shows its associated with poor overall survival (OS) in many tumor types, including metastatic castration-resistant prostate cancer (mCRPC).2


The CARD study (NCT02485691)3 evaluated cabazitaxel vs. abiraterone or enzalutamide in patients with mCRPC who previously received docetaxel and progressed within 12 months on the alternative androgen-signaling-targeted inhibitor (ARTA) (Figure 1). This study demonstrated that cabazitaxel was associated with improved radiographic progression-free survival (rPFS), OS, prostate-specific antigen (PSA) response, and tumor response when compared to abiraterone or enzalutamide (Figure 2).

Figure 1 – CARD study:

ESMO_CARD_study.png



Figure 2 – CARD study key endpoints:

ESMO_CARD_endpoints.png



In the presented study, the authors aimed to evaluate NLR as a predictive and prognostic biomarker in patients receiving cabazitaxel vs. abiraterone or enzalutamide in the CARD study. NLR was a pre-specified prognostic factor, and analysis of the association between baseline NLR and the primary endpoint (rPFS) was pre-planned in the study protocol. However, the analyses of the association between NLR, OS, PSA response, and time to PSA progression were post hoc. The association between baseline NLR and OS was investigated using stratified multivariate Cox regression with stepwise selection of covariates, including adjustment for treatment arm. The median NLR (n = 3.38) was selected as the cut-off threshold, as additional exploratory analyses did not provide strong evidence for an alternative optimal threshold.

Table 1 shows patient baseline characteristics by NLR groups (lower and higher than the median). Table 2 shows the multivariable analyses (including both treatment arms) showing the association of NLR with all studied endpoints. These analyses showed that high NLR at baseline, low hemoglobin, and high PSA at baseline was associated with worse OS. In the presence of these factors, cabazitaxel significantly improved OS (HR 0.628, p=0.022), as shown in Figure 3. Additionally, Figures 4, and 5 show rPFS and time to PSA progression by baseline NLR, respectively.

Table 1- Patient baseline characteristics:

ESMO_CARD_characteristics.png

Table 2- Multivariable analysis:

ESMO_CARD_analysis.png



Figure 3 – Overall survival by baseline NLR:

ESMO_Overall_survival.png



Figure 4 – rPFS by baseline NLR:

ESMO_rPFS.png



Figure 5 – Time to PSA progression by baseline NLR:

ESMO_CARD_PSA_progression.png

Importantly, PSA response by baseline NLR was maintained irrespective of the patient baseline NLR (Figure 6).

In summary, high NLR at baseline was shown to predict poor outcomes with abiraterone or enzalutamide in patients with mCRPC previously treated. However, NLR does not seem to be associated with outcomes for cabazitaxel. Interestingly, patients with high NLR at baseline, who were treated with abiraterone or enzalutamide, had a significantly shorter OS compared with those with low NLR at baseline. In contrast, OS did not significantly differ between patients with low and high NLR treated with cabazitaxel. In patients with high NLR at baseline, rPFS with cabazitaxel was almost three times longer than with abiraterone or enzalutamide. PSA response and time to PSA progression benefits that were seen with cabazitaxel were maintained irrespective of baseline NLR.

These results support the use of cabazitaxel over a second ARTA in previously treated mCRPC patients, and this was more pronounced in patients with high NLR at baseline.

Figure 6 – PSA response by baseline NLR:

ESMO20_baseline_NLR.png



Presented by: Ronald De Wit PhD Professor, Department Medical Oncology, Division Lead Genito-Urinary Clinical Research, Rotterdam, Netherlands

Written by: Hanan Goldberg, MD, MSc., Assistant Professor of Urology, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.

References:

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
  2. Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis. JNCI: Journal of the National Cancer Institute 2014; 106(6).
  3. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. New England Journal of Medicine 2019; 381(26): 2506-18.
Related Content:

ESMO Virtual Congress 2020: Cabazitaxel Activity in Men with Metastatic Castration-Resistant Prostate Cancer with and without DNA Damage Repair Defects
The Clinical Implications of The Efficacy and Safety in Older Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Cabazitaxel versus Abiraterone or Enzalutamide In The CARD Trial - William Oh and Stephen Freedland
CARD Study Demonstrates Cabazitaxel Improves Pain and Health-Related Quality of Life Analysis in Patients with mCRPC - Karim Fizazi 
Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer - Beyond the Abstract
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