A multidisciplinary panel of experts has issued guidelines that consolidate current evidence on testing for molecular biomarkers in colorectal cancer. The guidelines aim to standardize molecular testing for patients with colorectal cancer and help clinicians identify patients most likely to benefit from targeted treatments.

Biomarker testing is becoming standard practice for colorectal cancer, but it can be difficult for oncologists to decide which tests have the most potential to affect patient outcomes. To address that challenge, a new guideline consolidates the latest evidence and identifies which biomarkers best inform patient care.

The recommendations, developed by a panel of experts from the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology, includes 21 guideline statements based on a review of evidence from more than 4,000 studies.

“This guideline provides a snapshot of what we currently do and don't know about using biomarkers to guide treatment of colorectal cancer,” says Carmen Allegra, MD, chief of oncology and hematology at the University of Florida in Gainesville and a co-chair of the panel. “This should make it easier for physicians to know which tests to order and what to do with the findings.”

Most likely to affect practice are recommendations that involve testing for RAS and BRAF mutations. Mutations in KRAS, NRAS, and BRAF together occur in more than half of all colorectal cancer cases and are often associated with negative responses to the EGFR inhibitors cetuximab (Erbitux; Bristol-Myers Squibb) and panitumumab (Vectibix; Amgen).

Specifically, the panel recommends:

  • Cetuximab and panitumumab should be prescribed only for patients with metastatic colorectal cancer with no known RAS-activating mutations.

  • Patients with mismatch repair–deficient tumors should be tested for BRAF V600E mutations.

  • Clinicians should order mismatch repair–status testing to identify patients at high risk for Lynch syndrome.

“The guideline is clear that we should not be giving EGFR inhibitors to patients with RAS mutations and that patients with BRAF V600E mutations have a much worse prognosis” than those with nonmutated BRAF, says Michael Overman, MD, associate professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, who was not involved in developing the recommendations. “Knowing about these predictive and prognostic indicators helps guide our approach to therapy and helps to set patient expectations.”

The panel notes that other tests—such as the use of liquid biopsies to identify disease recurrence, detect emerging tumors, and test for RAS mutations—and predictive biomarkers are of potential interest but are not backed by enough evidence to warrant changing practice.

“This guideline consolidates the data that's out there and lays a clear framework for clinicians,” says Overman. “While we could test for a lot of biomarkers, this document clearly lays down which ones have the most potential to impact the management and survival of our patients.” –Janet Colwell

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.