588P - Is the derived neutrophil to lymphocyte ratio (dNLR) an independent prognostic marker in patients with metastatic colorectal cancer (mCRC)? Analysi...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Colon and Rectal Cancer
Presenter Connie Diakos
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors C.I. Diakos1, D. Tu2, V. Gebski3, S. Yip3, K. Wilson3, C.S. Karapetis4, C.J. O'Callaghan5, J. Shapiro6, N. Tebbutt7, D.J. Jonker8, L.L. Siu9, R. Wong10, C. Doyle11, A.H. Strickland12, T.J. Price13, J. Simes3, S. Clarke14
  • 1Kolling Institute Of Medical Research, Royal North Shore Hospital, 2065 - St Leonards/AU
  • 2Department Of Mathematics And Statistics, Canadian Cancer Trials Group, Queens University, Kingston/CA
  • 3Nhmrc Clinical Trials Centre, NHMRC Clinical Trials Centre University of Sydney, 2050 - Camperdown/AU
  • 4Department Of Medical Oncology, Flinders Centre for Innovation in Cancer, Flinders University and Flinders Medical Centre, Bedford Park/AU
  • 5Department Of Public Health Sciences, Canadian Cancer Trials Group, Queens University, K7L 3N6 - Kingston/CA
  • 6Department Of Medicine, Monash University, Melbourne/AU
  • 7Medical Oncology, Austin Hospital, 3084 - Heidelberg/AU
  • 8Department Of Medicine, Division Of Medical Oncology, Ottawa Hospital Research Institute, University of Ottawa, K1H8L6 - Ottawa/CA
  • 9Department Of Medical Oncology And Hematology, Princess Margaret Hospital, Toronto/CA
  • 10Hematology And Oncology, St. Boniface General Hospital Cancercare Manitoba, R2H 2A6 - Winnipeg/CA
  • 11Laval University, Centre Hospitalier Universitaire de Quebec, Quebec City/CA
  • 12Monash Cancer Centre, Monash University and Monash Cancer Centre, Melbourne/AU
  • 13Haematology And Oncology, The Queen Elizabeth Hospital and University of Adelaide, 5011 - Adelaide/AU
  • 14Medical Oncology, Royal North Shore Hospital, 2065 - St Leonards/AU

Abstract

Background

dNLR (neutrophil count /(total white cell - neutrophil count)) has shown prognostic utility for overall survival (OS) in a number of cancers. The CCTG/AGITG CO.17 and CO.20 studies examined the EGFR inhibitor, cetuximab (C), versus best supportive care, and in combination with the VEGF/FGFR inhibitor brivanib (B) or placebo, respectively, in previously treated patients with mCRC. Here, we examine dNLR in CO.17 and CO.20 for its utility to predict progression free survival (PFS), response rate (RR) and OS.

Methods

Association between dNLR status and PFS, OS and RR was analysed using multivariate regression models adjusting for baseline (BL) disease and patient (pt) characteristics. Interaction between treatment and dNLR status was studied by including an additional interaction term in the models.

Results

CO.17 recruited 572 pts; 570 pts had available BL dNLR data. CO.20 recruited 750 pts; 718 had BL data available. In both, pts with high BL dNLR (≥2) were significantly more likely to have poorer ECOG status, received more lines of therapy, abnormal alkaline phosphatase levels, ≥ grade 1 anaemia, ascites, presented with lung metastases, have ≥2 sites of metastases. Multivariate analyses results are summarised in Table 1. Both studies showed pts with high dNLR had significantly shorter OS. Significant association of dNLR status with PFS was only found in CO.20 but no significant association with RR was found in either study. Significant association was found with OS in all four treatment groups, but for PFS, in C + B arm of CO.20 only. In both studies, no significant interaction was found between dNLR status and treatment for either OS or PFS.

Multivariate analysis of dNLR in CO.17 and CO.20

CO.17 CO.20
dNLR

Conclusions

The dNLR has independent prognostic utility for OS in previously treated patients with mCRC. This provides a simple, inexpensive prognostic biomarker for heavily pre-treated mCRC patients and should be considered as a stratification factor in future clinical trials.

Clinical trial identification

Clinicaltrials.gov CO.20: NCT00640471 CO.17: NCT00079066

Legal entity responsible for the study

Canadian Cancer Trials Group Australian Gastro-Intestinal Trials Group

Funding

CO.17: lead sponsor - Canadian Cancer Trials Group; co-sponsor - Australian Gastro-Intestinal Trials Group; funder - Bristol-Myers Squibb. CO.20: lead sponsor - Canadian Cancer Trials Group; co-sponsor - Australian Gastro-Intestinal Trials Group; funder - Bristol-Myers Squibb.

Disclosure

C.I. Diakos: Ipsen Aadvisory Board, November 2015 & April 2016. V. Gebski: Honoraria: Sirtex. Consultancy: Sirtex. Travel support: Sirtex. C.S. Karapetis: Advisory Board Merck, Amgen. N. Tebbutt: Advisory Board Roche, Merck Serono. L.L. Siu: Research funding from Bristol Myers Squibb for clinical trials conduct. T.J. Price: Advisory Board Merck. S. Clarke: Advisory Board Roche, Merck. All other authors have declared no conflicts of interest.