522PD - Development and validation of a robust molecular diagnostic test (COLOPRINT) for predicting outcome in stage II colon cancer patients

Date 29 September 2012
Event ESMO Congress 2012
Session Gatrointestinal tumors, colorectal
Topics Diagnostics
Colon Cancer
Rectal Cancer
Presenter Thomas Bachleitner-Hofmann
Authors T. Bachleitner-Hofmann1, I. Simon2, R. Salazar3, J. Tabernero4, R. Rosenberg5, J. van der Akker6, Y. Li7, B. Chan7, G. Lanza8, A. Glas6
  • 1Surgery, Medical University of Vienna, 1090 - Vienna/AT
  • 2Research And Development, Agendia NV, 1098 XH - Amsterdam/NL
  • 3G-i Unit. Medical Oncology Dpt., Institut Catal, ES-08907 - Barcelona/ES
  • 4Oncology Department, Vall d'Hebron University Hospital, ES-08035 - Barcelona/ES
  • 5Department Of Surgery, Klinikum Rechtas der Isar, Munich/DE
  • 6Product Support, Agendia NV, 1098 - Amsterdam/NL
  • 7Product Support, Agendia Inc, 92618 - Irvine/US
  • 85istituto Di Anatomia E Istologia Patologica, University di Ferrara, Ferrara/IT

Abstract

Background

Only between 25 to 35% of stage II and IIIA colon cancer patients will experience a relapse of their disease and may benefit from adjuvant chemotherapy. ColoPrint is a gene expression classifier that can predict disease relapse in patients with early-stage colorectal cancer and helps to identify patients with higher risk of relapse.

Methods

ColoPrint was developed using whole genome expression data and was validated in public datasets and an independent patient cohort of 206 patients (Salazar et al., JCO 2011). The signature was translated to a customized 8-pack microarray. Positive and negative hybridization control genes monitor the quality of hybridization and a colon specific normalization gene set (n = 461) guarantee reliability of results. Reproducibility and precision studies with 20 times 6 samples were performed by multiple operators on multiple days. Additional independent patient cohorts were validated on the customized arrays. Uni- and multi-variate analyses were performed on the pooled stage II patient set (n = 320), the subset of T3/ MSS patients (n = 227) and stage IIIA (n = 16).

Results

The prognostic classifier was evaluated in reproducibility and stability assays and stringent quality controls were established following the successful lead of the FDA-cleared MammaPrint assay. Results of all tests met the pre-set criteria. In the analysis of all stage II and IIIA patients, ColoPrint classified two-third of patients as being at low risk. The 3-year Relapse-Free-Survial (RFS) RFS was 92% and 77% for low and high risk patients respectively with a HR of 2.9 (p = 0.001). Clinical and pathological risk parameters from the NCCN guidelines can be combined with ColoPrint for even more personalized risk assessment. ColoPrint is also able to distinguish risk groups in the subgroup of patients with T3 and MSS phenotype (HR= 2.7, p = 0.01) and IIIA (HR= 3.6, p = 0.08).

Conclusions

ColoPrint was technically and clinically validated and is now available for diagnostic use. ColoPrint significantly improves prognostic accuracy, thereby facilitating the identification of patients at higher risk who might be considered for additional treatment.

Disclosure

I. Simon: Employee of Agendia (maker of ColoPrint).

J. van der Akker: Employee of Agendia (maker of ColoPrint).

Y. Li: Employee of Agendia (maker of ColoPrint).

B. Chan: Employee of Agendia (maker of ColoPrint).

A. Glas: Employee of Agendia (maker of ColoPrint).

All other authors have declared no conflicts of interest.