Abstract 345P
Background
Proper patient selection for palliative chemotherapy is essential in patients with metastatic colorectal cancer (mCRC). C-reactive protein (CRP) and the derived neutrophil-to-lymphocyte ratio (dNLR) are available in clinical practice and may support prognostic understanding and decision-making. We studied the prognostic value of systemic inflammation through CRP, dNLR, Interleukin (IL)-6, and YKL-40 on progression-free survival (PFS) and overall survival (OS) in the NORDIC9 cohort including vulnerable older adults with mCRC.
Methods
The randomized NORDIC9-study included patients ≥70 years with mCRC not candidates for standard full-dose combination chemotherapy. Participants were allocated to receive either full-dose S1 or a dose-reduced combination of S1 plus oxaliplatin. Blood samples were collected at baseline and biomarkers were dichotomized according to standard cut-offs. Multivariable analyses adjusted for age, sex, ECOG performance status, and treatment allocation; furthermore, C-statistics were estimated.
Results
In total, 160 patients (82 men and 78 women) were included from 2015 to 2017. The median age was 78 years (IQR: 76-81). All investigated biomarkers were significantly elevated in patients with either weight loss, ≥3 metastatic sites, or having primary tumor in situ. In multivariable analyses for OS, all markers demonstrated statistically significant differences, with the highest HR observed for CRP (HR=3.30, 95% CI: 2.16-5.04, p<0.001 (Table). Regarding PFS, statistically significant differences were found for CRP, dNLR, IL-6, but not for YKL-40. Applying C-statistics, CRP indicated a good correlation for OS (AUC=0.72). Table: 345P
Progression-free and overall survival according to biomarkers of systemic inflammation multivariable analyses
| Biomarker | n | Progression-free survival | Overall survival | ||||||
| Hazard ratio | 95% CI | p-value | Harrell’s C | Hazard ratio | 95% CI | p-value | Harrell’s C | ||
| CRP (mg/L) | |||||||||
| ≤ 10 | 66 | 1.00 | 0.004 | 0.66 | 1.00 | <0.001 | 0.72 | ||
| > 10 | 86 | 1.64 | 1.17-2.30 | 3.30 | 2.16-5.04 | ||||
| dNLR | |||||||||
| ≤ 2.2 | 79 | 1.00 | 0.031 | 0.63 | 1.00 | 0.001 | 0.66 | ||
| > 2.2 | 78 | 1.43 | 1.03-1.98 | 1.91 | 1.31-2.80 | ||||
| IL-6 (pg/L) | |||||||||
| ≤ 4.5 | 47 | 1.00 | 0.008 | 0.64 | 1.00 | 0.045 | 0.65 | ||
| > 4.5 | 81 | 1.71 | 1.15-2.53 | 1.58 | 1.01-2.48 | ||||
| YKL-40 (μg/L) | |||||||||
| ≤ 200 | 72 | 1.00 | 0.061 | 0.63 | 1.00 | 0.005 | 0.66 | ||
| > 200 | 56 | 1.44 | 0.98-2.12 | 1.85 | 1.20-2.86 |
Conclusions
CRP is an easily available biomarker, which may support therapeutic decision-making in vulnerable older patients with mCRC.
Clinical trial identification
EudraCT (reg. no. 2014-000394-39).
Editorial acknowledgement
Legal entity responsible for the study
Department of Oncology, Odense University Hospital.
Funding
This investigator-initiated study was partly funded by Taiho Pharmaceuticals, Nordic Group, The Danish Cancer Society, the Academy of Geriatric Cancer Research (AgeCare), The Swedish Cancer Society, and the Region of Southern Denmark. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Disclosure
All authors have declared no conflicts of interest.