Liquid Biopsies Detect Minimal Residual Disease in Colorectal Cancer

DNA

Two different types of liquid biopsies—plasma and urine—can detect the number of copies of theKRASmutation in circulating DNA in patients with colorectal cancer who have resectable liver metastases with near 100% concordance with tissue biopsies, according to a pilot study presented at the 2015 Annual Meeting of the American Association for Cancer Research (AACR).

“This study suggests that urinary and plasmaKRASin circulating DNA can be used to detect minimal residual disease in patients with metastatic colorectal cancer,” said study co-author Cecile Rose T. Vibat, PhD, senior director of translational science & clinical affairs at Trovagene, San Diego, CA, the company that has developed and will market these tests.

Several other companies currently have plasma DNA mutational assays, but Trovagene is the only company with a urinary test, according to a company spokesperson.

The study enrolled 20 patients with stage IV colorectal cancer who had tissue biopsies at baseline and had knownKRASmutations. All patients were undergoing surgical treatment in combination with systemic therapies, including neoadjuvant radio/chemotherapy, adjuvant chemotherapy, and adjuvant targeted therapy. Archived urine and plasma samples (total of 190) were collected at baseline prior to surgery and at various intervals throughout the course of disease.

100% of the plasma samples and 86% of the urine samples had sufficient DNA to be evaluable.

Using the liquid biopsies, a correct KRAS mutation was identified in 95% of archival plasma and 92% of archival urine specimens. Concordance betweenKRASidentified in tissue biopsy and that for liquid biopsies was 100% when both urine and plasma assays were analyzed.

Vibat noted that the degree of DNA degradation in archived samples of urine is significantly elevated compared with typical clinical samples obtained in real time.

In 4 of 5 patients with curative intent surgery,KRASlevels were undetectable in urine or plasma at all timepoints postsurgery, whereas theKRASsignal remained detectable after surgery with palliative intent for 10 of 12 patients in urine and 9 of 12 patients with plasma.

A larger cohort of patients will be studied using the liquid biopsies (urine and plasma) to determine the prognostic significance of postsurgicalKRASlevels and overall survival in the stage IV colorectal cancer patients with liver metastases.

• Melnikova V, Poole JC, Vibat CRT, et al. Monitoring minimal residual disease by urinary or plasma circulating tumor DNA ofKRASmutation burden in colorectal cancer patients with resectable liver metastases. Presented at the 2015 Annual Meeting of AACR. Philadelphia, PA. April 22, 2015. Abstract 5237.