Abstract 637P
Background
The NLR could be established as an important prognostic marker for the outcome of mCRPC patients treated with chemotherapy, steroids and novel androgen receptor directed therapies. Thus far the value of the NLR as a biomarker in the context of therapeutic radionuclides has never been explored.
Methods
The pivotal phase III trial of Ra-223 in mCRPC (ALSYMPCA) randomly assigned 921 patients, to Radium-223 or matching placebo in a 2:1 ratio. The primary endpoint was overall survival (OS). This post-hoc analysis investigated the role of NLR, neutrophilia (defined as an absolute neutrophil count > 7000 G/L) and lymphopenia (defined as an absolute lymphocyte count < 1.000 G/l) on the outcome of mCRPC patients treated with Ra-223 (n = 613). OS was analyzed using Kaplan-Meier estimates and Cox proportional hazard models. Nominal p-values were determined by log-rank tests.
Results
In the intention-to-treat population NLR ≥ 3, NLR ≥ median and log transformed NLR were associated with a significantly shorter OS. Lymphopenia showed an even stronger association with OS and a median survival disadvantage of 6 months, while neutrophilia did not show any association with the outcome of Ra-223 treatment. Patients with a prognostically detrimental NLR ≥ 3 had the worst OS [HR 1.56 (95% CI 1.15 – 2.12)] when accompanied by additional lymphopenia compared to all other constellations of NLR ≥ 3. Table: 637P
| Cut-off | Median OS, months | Univariate analysis | Multivariate analysis# | |
| NLR | ≥ 3 | 13.1 | HR 1.58, p < 0.001 | HR 1.31, p = 0.028 |
| < 3 | 17.2 | |||
| NLR | ≥ median | 12.9 | HR 1.56, p < 0.001 | HR 1.29, p = 0.034 |
| < median | 17.0 | |||
| NLR | Log-transformed* | HR 1.35, p < 0.001 | HR 1.16, p = 0.029 | |
| Neutrophilia | Yes | 15.3 | HR 1.01, p = 0.945 | HR 1.04, p = 0.790 |
| No | 14.7 | |||
| Lymphopenia | Yes | 10.1 | HR 1.85, p < 0.001 | HR 1.49, p = 0.002 |
| No | 16.1 |
*Log-transformed using base 2 so that HR associated with a unit change in log NLR represents a doubling of the NLR #Variables: total ALP, current use of bisphosphonates, prior use of docetaxel, pain at baseline, ECOG, extend of disease grading, baseline albumin, log LDH, log PSA, age
Conclusions
A high NLR is associated with a poorer OS in mCRPC patients treated with Ra-223 independently of the cut-off used. Lymphocytes seem to be the leucocyte subtype that has the strongest association with prognosis.
Clinical trial identification
NCT00699751.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bayer Healthcare.
Disclosure
A. Meisel: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck-Serono; Research grant/Funding (institution): Merck & Cie; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy: Takeda; Advisory/Consultancy: Vifor. C. Parker: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen. R. Kühne: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Roche. O. Sartor: Advisory/Consultancy: Advanced Accelerator Applications; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Astellas; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Bellicum; Advisory/Consultancy: Blue Earth Diagnostics, Inc.; Advisory/Consultancy: Bravarian Nordic; Advisory/Consultancy: Bristol-Meyers-Squibb; Advisory/Consultancy: Clovis Oncology, Inc.; Advisory/Consultancy: Constellation; Advisory/Consultancy, Research grant/Funding (institution): Dendreon; Advisory/Consultancy: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution): Invitae; Advisory/Consultancy, Research grant/Funding (institution): Janssen Biotech, Inc.; Advisory/Consultancy: Myriad; Advisory/Consultancy: Noxopharm; Advisory/Consultancy: Progenics; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Endocyte; Research grant/Funding (institution): Innocrin; Research grant/Funding (institution): SOTIO. F. Stenner-Liewen: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): BMS; Honoraria (institution), Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Sanofi.