Abstract 5555
Background
In RAS wild type metastatic colorectal cancer patients (pts), high tumor expression of microRNA miR-31-3p and miR-31-5p has been associated with poorer benefit of anti-EGFR therapy. miR-31-3p expression has been shown to be predictive of treatment effect in the FIRE-3 trial. The PETACC-8 phase III trial assessed the efficacy of cetux addition to FOLFOX compared to FOLFOX only in pts with resected stage III colon cancer (CC). The primary end point was negative, but a trend towards benefit of cetux on disease free survival (DFS) was observed in pts with RAS/BRAF wild type (WT) tumors. The current study aimed at assessing miR-31-3p and 5p tumor levels as prognostic and predictive biomarkers of adjuvant cetux benefit in these pts.
Methods
miR-31-3p and 5p levels were measured by RT-qPCR from 477 WT pts tumor RNA. The primary objective was to demonstrate a benefit of cetux on DFS for low miR-31-3p expressers. Cox regression model was used for univariate and multivariate analyses. Optimal cut-off values for low and high expressers were determined post hoc.
Results
In the studied population, cetux benefit was significant for DFS (HR = 0.71 [0.50;1.00] p = 0.05) but not for Overall Survival (OS) (HR = 0.79 [0.53;1.18] p = 0.25). Expression of miR-31-3p and miR-31-5p were highly correlated (R > 0.9). Higher miR-31-3p and 5p expression were associated with shorter DFS and OS (p < 0.01). Pts with low miR-31-3p levels (n = 218/435, 50%) had a non-significant benefit from cetux on DFS (HR 0.61 [0.33; 1.11] p = 0.10) and OS (HR = 0.67 [0.33; 1.35] p = 0.26). Pts with low miR-31-5p levels (n = 233/477, 49%) benefited from cetux on DFS (HR = 0.46 [0.25; 0.84] p = 0.01) and OS (HR = 0.50 [0.25; 0.99], p = 0.047) whereas high expressers did not (DFS: HR = 0.87 [0.56; 1.34] ; OS: HR = 1.01 [0.61; 1.67]). miR-31-5p was predictive of treatment effect on DFS at the 10% level (interaction tests: p = 0.09 for DFS and p = 0.103 for OS). Results were still significant after adjustment for clinical covariates.
Conclusions
In pts with resected stage III WT CC, miR-31-3p and 5p were prognostic of DFS and OS. Pts with low miR-31 expression benefited from cetux addition to FOLFOX for adjuvant therapy, and miR-31-5p was predictive of cetux efficacy.
Clinical trial identification
NCT03362684.
Legal entity responsible for the study
IntegraGen SA.
Funding
IntegraGen.
Editorial Acknowledgement
Disclosure
Y. Gaston Mathe: Ex employee: IntegraGen. S. Martin-Lannerée, C. Vazart, K. Fontaine: Employee: IntegraGen. A. Caumont, F. Montestruc: Consultant: IntegraGen. J. Taieb: Honoraria: Lilly, Celgene, Servier, Amgen, Roche, Merck, Sirtex, Sanofi. P. Laurent-Puig: Honoraria: IntegraGen, Merck-Serono, Amgen, Boehringer-Ingelheim, Roche, Lilly, Sanofi. All other authors have declared no conflicts of interest.
Resources from the same session
1159 - Molecular characterization and search for founding effects in Canarian families with Hereditary Breast and Ovarian Cancer Syndrome
Presenter: Elisenda Llabres Valenti
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3725 - Effect of the polymorphism rs2066844 of the NOD2 gene on colon cancer incidence in a high cardiovascular risk population. Modulation by gender
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3708 - Effect of the polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a high cardiovascular risk population
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5057 - Association of a genetic variant in cyclin-dependent kinase Inhibitor 2A gene with the increased risk of breast cancer
Presenter: Soodabeh Shahid Sales
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5970 - Investigating the role of HAT protein TIP60 in regulating functional dynamics of nuclear receptor PXR
Presenter: KARISHMA BAKSHI
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1360 - The role of downregulated SIRT3 expression in patients with hepatocellular carcinoma
Presenter: Hanhee Jo
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1634 - Prediction and Intervention of Colorectal Cancer Risk with Artificial Intelligent System
Presenter: Yang Ge
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4921 - Measuring the Efficiency of Cancer Care in Europe
Presenter: Rikard Althin
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1235 - Circulating cell-free DNA isolated from plasma of mesenteric veins predicts prognosis in stage II colorectal cancer patients
Presenter: Chih-Yung Yang
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5169 - _lonality of uterine carcinosarcoma as a factor of clinical prognosis.
Presenter: Natalia Levitskaya
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract