The neutrophil–lymphocyte ratio (NLR) is recognized as a prognostic marker in many cancers, including metastatic castration-resistant prostate cancer (mCRPC). In this study, we perform a retrospective analysis of the pivotal COU302 study of abiraterone acetate (AA) as first line therapy for men mCRPC.
The COU302 study randomized men with minimally symptomatic mCRPC to 1000mg AA once daily plus 5mg prednisone (AA + P) twice daily or placebo plus 5mg prednisone (P) twice daily. We utilized Kaplan–Meier survival and cox proportional hazard analyses to assess the effect of baseline NLR on response to AA + P versus P. Adjustment co-variates were selected from a recently reported analysis of the PREVAIL study of enzalutamide in men with mCRPC. Based on this analysis, we selected a NLR cut-off value of 2.5. Outcomes assessed included the co-primary endpoints from the COU302 study overall survival (OS) , radiographic progression free-survival (RPFS) and PSA progression-free survival (PFS).
Among the 1088 patients in the COU302 study, baseline NLR values showed significant differences according to baseline albumin below median (3.16 vs 2.92, p = 0.011), but no other baseline covariates. Mean NLR significantly increased following treatment initiation and at the end of study compared to baseline. Among patients with a baseline NLR ≥2.5, there was similar OS in AA + P and P treatment arms (p = 0.26), which was confirmed on adjusted cox proportional hazards (AA +P HR 0.95, p = 0.65). AA + P showed a significant OS benefit versus P (p = 0.0011) in men with baseline NLR <2.5, with an adjusted HR of 0.723(p = 0.012). For RPFS, benefits for AA + P were seen in men with NLR <2.5 or ≥ 2.5, with the magnitude of benefit greater in men with NLR <2.5. In the AA + P arm, men with baseline NLR <2.5 had significantly better PSA PFS compared to baseline NLR ≥2.5 (p = 0.03); no significant differences were seen in men in the placebo arm.
In the COU302 study, we observed that patients with a screening NLR<2.5 had a significant benefit to AA + P compared to P, whereas for patients with a screening NLR ≥2.5, this benefit was less evident. Increases in the NLR value from baseline could not be used to predict response to AA.
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V. Fradet: Speaker: Abbvie, Bayer, Ferring, Janssen, Sanofi; Consultant: Amgen, AstraZeneca, Astellas, Bayer, Ferring, Janssen, Sanofi; Adviser: Amgen, Astellas, Bayer, Ferring, Janssen, Sanofi; Research grant: Amgen, AstraZeneca, Astellas, Janssen, Sanofi; Clinical trial: AstraZeneca, Bayer, Janssen; Meeting sponsor: Bayer, Janssen, Lilly; Educational grant: Janssen. P. Toren: Scientific study or trial: Innocrin Pharma, Roche; Consultant, Advisor: Sanofi Canada, Ferring, Astellas, Abbvie. All other authors have declared no conflicts of interest.