CIMP biomarker
Research suggests that CIMP provides prognostic information in patients with colorectal cancer, according to Dr. Grady. But it also may predict benefit from the addition of irinotecan to 5-fluorouracil and leucovorin in patients with stage III disease having intact mismatch repair (Gastroenterology. 2014;147[3]:637-45).
“CIMP is a potentially emerging marker for the use of cytotoxic agents, probably the most promising one today,” he commented.
Extended RAS assay
The extended RAS assay, which evaluates the whole exome for mutations in both KRAS and NRAS, is useful for guiding decisions about therapies that target signaling through the epidermal growth factor receptor (EGFR), such as panitumumab (Vectibix). However, its value is mainly limited to identifying patients who will not respond to this therapy, according to Dr. Grady.
By incorporating NRAS, this combination assay picks up an additional 10% of patients who will not respond to anti-EGFR therapy (J Clin Oncol. 2015;33[7]:682-5). But even so, it identifies only about a third of all nonresponders.
“We really need better biomarkers to identify patients who will respond, as well as identifying those patients who will not respond,” he said. “There is still a huge need for positive predictive biomarkers for the anti-VEGF [vascular endothelial growth factor] therapies and the anti-EGFR therapies, as well as for the cytotoxic therapies and the immune checkpoint inhibitors.”
Emerging biomarkers
The emerging colorectal cancer biomarkers include a variety of cancer genome mutation panels for assessing treatment options in patients with metastatic disease: OncoPlex, Foundation Medicine panels, and SNaPshot.
The clinical utility of these assays at present is still unclear. For example, the OncoPlex assay assesses tumors for 194 genes, only a subset of which are currently actionable or may be in the near future.
“Where you go with this is the real challenge,” Dr. Grady said. He referred clinicians to My Cancer Genome, a website managed by the Vanderbilt-Ingram Cancer Center that provides information about the specific mutations found with these panels.
The site additionally offers a concierge-like service called DIRECT (DNA-mutation Inventory to Refine and Enhance Cancer Treatment) that may be helpful in individual cases. “That [service] will identify what the response for tumors that have specific mutations has been in previous clinical trials and any clinical trials that are ongoing for which your patient may be a candidate,” he explained.
Dr. Grady disclosed that he is a patent holder of methylated MLH1 and receives consulting fees from Myriad Genetics.