Abstract 629P
Background
High NLR as a biomarker of inflammation is associated with poor overall survival (OS) in different malignancies, including mCRPC (Lorente et al, Ann Oncol 2015). The CARD study (NCT02485691) reported improved radiographic progression-free survival (rPFS) and OS with CBZ vs abiraterone or enzalutamide in patients with mCRPC who previously received docetaxel and progressed within 12 months on the alternative androgen receptor-targeted agent (ARTA) (de Wit et al, N Engl J Med 2019). This analysis of CARD evaluated the impact of baseline NLR on outcomes.
Methods
Multivariable Cox regression analysis with stepwise selection of covariates (stratification factors and pre-planned prognostic factors), including adjustment for treatment, was used to investigate the prognostic association between baseline NLR (as a continuous variable) and OS. The associations between baseline NLR (< vs ≥ median), and OS, rPFS, time to prostate-specific antigen (PSA) progression, and PSA response (confirmed PSA decline ≥ 50% from baseline) were also evaluated.
Results
Baseline median NLR in both arms overall was 3.38; higher baseline NLR independently associated with poor OS (HR [95% CI]: 1.05 [1.02–1.08]; p = 0.0003). Additional factors associated with poor OS were lower hemoglobin and high PSA at baseline. Greater clinical activity in terms of rPFS, time to PSA progression and PSA response was seen with CBZ irrespective of baseline NLR, with the benefits of CBZ vs ARTA particularly marked in patients with NLR ≥ median (Table). CBZ also significantly prolonged OS vs ARTA in patients with baseline NLR ≥ median (HR [95% CI]: 0.49 [0.30–0.81]; log-rank p = 0.004). Table: 629P
| NLR ≥ median | NLR < median | |||
| CBZ (n = 63) | ARTA (n = 60) | CBZ (n = 62) | ARTA (n = 61) | |
| Median rPFS, months (95% CI) | 8.5 (4.9–11.4) | 2.8 (2.7–4.5) | 7.5 (5.4–8.5) | 5.1 (3.1–7.0) |
| Median OS, months (95% CI)* | 15.3 (11.8–20.3) | 9.5 (9.0–11.8) | 12.9 (10.5–19.1) | 13.3 (9.3–17.3) |
| CBZ (n = 56) | ARTA (n = 52) | CBZ (n = 56) | ARTA (n = 50) | |
| Time to PSA progression, months (95% CI)* | 6.9 (3.5–10.3) | 2.1 (1.7–2.8) | 5.8 (3.5–8.8) | 2.1 (1.4–2.8) |
| PSA response, %* | 37.5 | 17.3 | 35.7 | 12.0 |
* Post-hoc analyses.
Conclusions
This present analysis of CARD confirms that NLR is prognostic for poor outcomes in mCRPC. The superiority of CBZ vs a second ARTA was particularly marked in patients with high baseline NLR.
Clinical trial identification
EudraCT: 2014-004676-29. Release date: 1 March 2019.
Editorial acknowledgement
Editorial assistance was provided by Annie Berkley and Amber Wood of MediTech Media, funded by Sanofi.
Legal entity responsible for the study
Sanofi Genzyme.
Funding
Sanofi Genzyme.
Disclosure
R. de Wit: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy: Roche/Genetech; Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Clovis Oncology; Travel/Accommodation/Expenses: Lily. D. Castellano Gauna: Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Bayer; Advisory/Consultancy: Lilly; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Boehringer Ingelheim. G. Kramer: Honoraria (self): Sanofi; Honoraria (self): Bayer; Honoraria (self): Takeda; Honoraria (self): Astellas Pharma; Honoraria (self): Janssen; Honoraria (self): Ipsen; Honoraria (self): AstraZeneca ; Honoraria (self): Novartis. J-C. Eymard: Honoraria (self), Leadership role: Sanofi. C.N. Sternberg: Advisory/Consultancy: Bayer; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Incyte; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Merck; Advisory/Consultancy: Medscape; Advisory/Consultancy: UroToday; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Bayer; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Incyte; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Merck; Advisory/Consultancy: Medscape; Advisory/Consultancy: UroToday; Advisory/Consultancy: Astellas Pharma. K. Fizazi: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: Sanofi; Advisory/Consultancy: Orion Pharma GmbH; Advisory/Consultancy: Curevac; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: ESSA; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen. B. Tombal: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Pharma; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Ferring; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: Takeda; Advisory/Consultancy: Steba Biotech; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Travel/Accommodation/Expenses: Ferring; Honoraria (self): Pfizer; Honoraria (self): Myovant Sciences. A. Bamias: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Ferring; Honoraria (self): Astellas Pharma; Honoraria (self): Sanofi; Honoraria (self): Debiopharm Roche. J. Carles: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy: J&J; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (self): Astellas Pharma; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (self): Sanofi; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Roche; Advisory/Consultancy: Asofarma ; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Roche ; Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (self): AB Science; Research grant/Funding (self): Aragon Pharmaceuticals; Research grant/Funding (self): Arog; Research grant/Funding (self): AVEO; Research grant/Funding (self): Blueprint Medicines; Research grant/Funding (self): BN ImmunoTherapeutics; Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): BMS; Research grant/Funding (self): Clovis Oncology; Research grant/Funding (self): Cougar Biotechnology; Research grant/Funding (self): Deciphera; Research grant/Funding (self): Exelixis; Research grant/Funding (self): Roche/Genentech; Research grant/Funding (self): GSK; Honoraria (self): Incyte; Research grant/Funding (self): Janssen-Cilag; Research grant/Funding (self): Karyopharm Therapeutics; Research grant/Funding (self): Medimmune; Research grant/Funding (self): Millennium; Research grant/Funding (self): Nanobiotix; Research grant/Funding (self): Novartis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Puma Biotechnology; Research grant/Funding (self): SFJ Pharmaceuticals Group; Research grant/Funding (self): Teva; Research grant/Funding (self): Mediolanum Laboratories Leurquin; Research grant/Funding (self): Lilly. R. Iacovelli: Honoraria (self): Sanofi; Honoraria (self): Janssen; Honoraria (self): Pfizer; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): BMS; Honoraria (self): MSD. B. Melichar: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: SERVIER; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Pfizer; Research grant/Funding (self): Novcartis; Research grant/Funding (self): Merck Serono. E. M. Poole: Full/Part-time employment: Sanofi. A. Ozatilgan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Sanofi. C. Geffriaud-Ricouard: Full/Part-time employment: Sanofi. J. de Bono: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas Pharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck Serono; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Sierra Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Menarini Silicon Biostystems; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Taiho Pharmaceuticals; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Genmab; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Orion Pharma GmbH; Advisory/Consultancy: Eisai and BioXCel therapeutics ; Travel/Accommodation/Expenses: Qiagen; Travel/Accommodation/Expenses: Vertex; Honoraria (self), Research grant/Funding (self): Astex Pharmaceuticals; Honoraria (self), Research grant/Funding (self): CellCentric; Honoraria (self), Research grant/Funding (self): MedImmune; Honoraria (self), Research grant/Funding (self): Medivation; Honoraria (self), Research grant/Funding (self): BioExcel. All other authors have declared no conflicts of interest.