Neutrophil-to-lymphocyte Ratio as a Predictive Marker of Response to Abiraterone Acetate: A Retrospective Analysis of the COU302 Study

Abstract

Background: The neutrophil-lymphocyte ratio (NLR) is an inexpensive and accessible prognostic marker for many cancers, including metastatic castration-resistant prostate cancer (mCRPC).

Objective: In this study, we assess the role of NLR as a predictive biomarker through a retrospective analysis of the pivotal COU302 study of abiraterone acetate (AA) as first-line therapy for men with asymptomatic or minimally symptomatic mCRPC.

Design, setting, and participants: The COU302 study randomized asymptomatic or minimally symptomatic men with mCRPC to receive AA plus prednisone or prednisone as first-line treatment. Baseline NLR, overall survival, radiographic progression-free survival, and prostate-specific antigen (PSA) progression-free survival were evaluated.

Outcome measurements and statistical analysis: Descriptive statistics, as well as Kaplan-Meier and Cox survival models were used to assess the effect of baseline NLR and changes in NLR on response to AA plus prednisone versus prednisone, with adjustment for important covariates.

Results and limitations: Among the 1082 patients who received treatment, baseline NLR values showed no significant differences according to baseline covariates except for albumin. Baseline variables were similar between dichotomous groups with an NLR cutoff of 2.5, except for a lower proportion of patients with >10 bone metastases in the NLR <2.5 group. Our survival results demonstrate that higher NLR values corresponded to poorer overall survival and PSA response to AA but not to placebo, which was confirmed in our adjusted regression models. No significant differences were seen in time to radiographic progression. In separate analyses, an increase or decrease in NLR by 2 from treatment baseline did not clearly signal subsequent lack of benefit with continued AA.

Conclusions: Our results suggest that baseline NLR may be able to predict response to AA in men with asymptomatic mCRPC but that changes in NLR during treatment are insufficient to guide treatment. Further validation studies are warranted.

Patient summary: In this report, we look at the ratio of circulating immune cells as a predictor of response to abiraterone acetate (AA), using data from a large trial. Our results suggest that this ratio derived from routinely obtained bloodwork can predict which patients respond better to AA.

Keywords: Abiraterone acetate; Biomarker; Castrate-resistant prostate cancer; Immune system; Inflammation; Neutrophil-lymphocyte ratio.