Leukocyte subtypes and myeloid derived suppressor cells as prognostic markers in metastatic castration resistant prostate cancer treated with cabazitaxel: A satellite study of the CABASTY phase III trial.

Abstract

126 Background: CABASTY trial investigated the benefit of an adapted schedule of cabazitaxel (16 mg/m2 bi-weekly versus 25 mg/m2 tri-weekly) in mCRPC patients previously treated with docetaxel and alternative androgen-targeted therapy. The study met its endpoints with a significantly decreased incidence of grade ≥ 3 neutropenia without a decrease in overall survival. This preplanned analysis evaluated the prognostic impact of neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelets ratio (NPR) myeloid derived suppressor cells (MDSC) and leukocyte subtypes counts in this setting. Methods: 44 patients treated with cabazitaxel were included. Peripheral blood mononuclear cells were isolated and myeloid compartment analysis were performed at baseline, week 6 (S6) and week 12 (S12) of treatment using a multi-parametric flow cytometry panel. We investigated at each timepoints the association of NPR, NLR, MDSC and leukocytes subtypes with PSA response rate (PSArr), Progression Free Survival, and Overall Survival with a preplanned uni- and multivariate analysis. Results: The NLR, NPR, MDSC subtypes and lymphocytes count at baseline were prognostic in the CABASTY trial regardless of the cabazitaxel regimen. Patients with a high lymphocyte count and/or a low NLR, NPR, and MDSC counts at baseline had a significantly improved PSAr, PFS and OS. In the multivariate analysis, a NPR > 1,84 and lymphocytes count < 1,2 G/L at baseline were significantly associated with OS [HR 2.007 (1.3 - 3.1)] and [HR 0.38 (0.20 - 0.73)]. Conclusions: High NLR, NPR, neutrophil and MDSC counts as well as a low lymphocyte count at baseline and during treatment predict poor outcomes in mCRPC patients treated with cabazitaxel. NPR and lymphocyte count are readily available biomarkers that may be useful for risk stratification in future clinical trials and could be incorporated into prognostic nomograms. Clinical trial information: NCT02961257 .