The miR-31now enables clinicians to identify patients for which first-line anti-EGFR treatment will be of greater clinical benefit versus anti-VEGF therapy or when second or further lines of treatment with anti-EGFR therapy is beneficial to patients with mCRC [1-4]. Low miR-31-3p expression levels predicts survival benefit with cetuximab in RAS wild-type (WT) metastatic colorectal cancer patients receiving FOLFIRI therapy.[4,5]

 

• Low miR-31-3p expression favors first-line treatment with cetuximab for RAS WT mCRC patients.[4,5]

• High miR-31-3p expressors have no difference in outcomes when treated with anti-EGFR or anti-VEGF therapy.[4,5]

• The RT-qPCR miR-31now test has been developed and technically validated to measure miR-31- 3p expression levels in FFPE specimens from metastatic colorectal cancer tumors.[6]

RESULTS FROM PROSPECTIVE-RETROSPECTIVE STUDY[4,5] 

miR-31-3p expression was measured in primary tumors from 340 RAS WT patients with metastatic colorectal cancer enrolled in the FIRE-3 trial. Patients were split into low or high miR-31-3p expression subgroups according to a pre-defined cut-off.
 
Results from the study demonstrated that RAS WT mCRC patients with low miR-31-3p expression treated with cetuximab had a:

•  40% risk reduction for death when treated with cetuximab compared to bevacizumab.
•  12 month longer median overall survival when treated with cetuximab versus bevacizumab.

There was no difference in survival outcomes between cetuximab and bevacizumab in patients with high miR-31-3p expression.
 

The results of this study demonstrate that low miR-31-3p expression levels predicts survival benefit with cetuximab in RAS WT metastatic colorectal cancer patients receiving FOLFIRI therapy.

Additional data from the study:

There was a significantly higher investigator-assessed objective response in patients with low miR-31-3p expression treated with cetuximab + FOLFIRI vs. bevacizumab + FOLFIRI.  OR = 4.49 [2.07 ; 9.76], p=0.0001
Odds ratio [95% CI] adjusted on age, number of organs and BRAF status. Excludes patients with missing data.

 
 
 
 
 
 




Depth of response (DoR) for patients treated with cetuximab + FOLFIRI was significantly correlated with miR-31-3p expression levels. 
There was no correlation observed between DoR and miR-31-3p expression in patients treated with bevacizumab + FOLFIRI.

 
 
 
 
 
 
 
Study conclusions:

•  Low miR-31-3p expression favors first-line treatment with cetuximab for RAS WT mCRC patients.
•  High miR-31-3p expressors have no difference in outcomes when treated with anti-EGFR or anti-VEGF therapy.
 
 
References:
1. Manceau G, Imbeaud S, Thiébaut R, et al. Clin Cancer Res. 2014; 20: 3338-47.
2. Pugh S, Thiébaut R, Bridgewater J, et al. Oncotarget. 2017: 8:93856-66.
3. Laurent-Puig P, Paget-Bailly S, Vernerey D, et al. J Clin Oncol. 2015; 33: (suppl; abstr 3547).
4. Laurent-Puig P, Grisoni ML, Heinemann V, et. al. J Clin Oncol . 2016; 34 (suppl; abstr 3516).
5. Data on file.
6. Ramon L, David C, Fontaine K, et al. Biomarker Insights. Published online March 16, 2018, https://doi.org/10.1177/1177271918763357