Biomarkers Help Personalize Metastatic Colorectal Cancer Treatment

In patients with metastatic colon cancer, response to first line chemotherapy is a strong predictor of overall survival (OS), but currently, oncologists lack diagnostic tests to determine which chemotherapy regimen offers the greatest chance for response in an individual patient.

The introduction of new cytotoxic and targeted agents for patients with metastatic colon cancer, (mCRC) has improved overall survival (OS) rates, with expected median survival now in excess of 20 months with many patients surviving beyond two years.

Scientists at the University of California San Diego (La Jolla, CA, USA) performed a retrospective analysis on two cohorts of patients with known excision repair cross-complementation group 1 gene (ERCC1) and tumor suppressor (TS) gene expression levels. Eighteen patients were male (44%) and 23 were female (56%). The median age was 57.6 years with range from 31 to 86 and 24 (59%) of the patients underwent surgery for the primary tumor and 12 (29%) underwent a metastatectomy during the course of their treatment.

Gene expression analysis for two genes, ERCC1 and TS was measured with the commercially available ResponseDX: Colon assay (Response Genetics; Los Angeles, CA, USA) in 41 patients with de novo metastatic colon cancer diagnosed between July 2008 and August 2013. The ResponseDX: Colon assay includes quantitative polymerase chain reaction (qPCR) to measure gene expression for ERCC1, TS, and Vascular Endothelial Growth Factor Receptors (VEGFR) as well as specific mutations. The threshold values for the normalized gene expression measurements used to stratify patients into high or low expression groups were 4.0 and 1.73 for TS and ERCC1, respectively.

The scientists found that found that 33 of their 41 patients had low ERCC1 levels. These same patients also had significantly longer average survival time of 36 months compared to patients with high ERCC1 levels at 10 months. Similarly, 29 patients had low TS levels and significantly longer average survival times of 36 months than patients with high TS levels at 15 months. From 22 of the 41 patients who had low levels of both ERCC1 and TS, 91% responded to oxaliplatin, suggesting that this should be the first treatment choice for patients with low ERCC1 and TS.

John Paul Shen, MD, senior clinical fellow, and co-first author said, “Our study is small, retrospective and all of the patients were located at a single medical center, but it demonstrates that it's possible to use molecular diagnostics to identify subgroups of patients more likely to respond to a given treatment. Given this proof-of-principle, it's our hope that molecular biomarkers will be included in future prospective clinical trials in metastatic colorectal cancer.” The study was published on June 17, 2015, in the journal Public Library of Science ONE.

Related Links:
University of California San Diego
Response Genetics