Microarray Gene Expression Study Of The Respect Trial For The Identification Of Prognostic And Predictive Markers.
JOURNAL OF CLINICAL ONCOLOGY(2013)
Abstract
e14561 Background: The RESPECT trial (n = 198) tested the addition of Sorafenib to standard mFOLFOX6 treatment in first line metastatic colorectal cancer (mCRC) patients but resulted in no statistical significant improvement in progression free survival, and no evidence for overall benefit. Sorafenib inhibits several Raf kinases (including B-Raf). Samples with high BRAF-mutant-like score were previously shown to identify a subset of colon tumors with a similar biology and outcome to BRAF mutant patients (Popovici et al. J. Clin. Oncol., 30(12):1288–95, 2012). Methods: A subset of 125 patients from the trial was available for gene expression analysis from their primary tumor FFPE samples, using the Colon DSA gene expression arrays from Almac. Mutation status for KRAS and BRAF was previously assessed. The potential prognostic and/or predictive effect of a high BRAF-mutant-like score was assessed. The analyses were performed using Cox proportional hazards regression models and Kaplan-Meier curves. The logrank test was used to compare the survival distributions (significance level: 5%). Results: Molecular profiling was performed on FFPE tissue samples from primary tumors of 125 mCRC patients, 95 samples (47 in the combined arm; 3 BRAF mutants) were successfully processed. Limitations in amount of material available in this retrospective analysis led to failure to reach the required RNA amount for amplification in 30 samples (dropout rate = 24%). The collected gene expression data was of good quality: all 95 array profiles could be used (10 were flagged for slightly inferior quality). The BRAF-mutant-like score was recognized as marker of poor OS in a Cox regression model (HR = 1.55 [95% CI: 1.12 - 2.13], 1 unit = 1 IQR, P = 0.007). The HR difference between the two arms (combined arm: HR = 1.36; reference arm: HR = 1.41) is not significant. Conclusions: The poor survival of metastatic colorectal cancer patients with a BRAF-mutated-like tumor is confirmed, but no predictive effect was found. FFPE tissues are well-suited for this kind of study and allow to accurately test the hypotheses of interest. Further analyses are planned to generate hypotheses about markers of sensitivity to mFOLFOX6 or Sorafenib.
MoreTranslated text
Key words
Metastatic Colorectal Cancer,BRAF Mutations,KRAS Mutations,Cancer Risk
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined