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September 2016

Adjuvant Therapy for Colon CancerSmall Steps Toward Precision Medicine

Author Affiliations
  • 1Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota
  • 2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
JAMA Oncol. 2016;2(9):1133-1134. doi:10.1001/jamaoncol.2016.2304

In current practice, the choice of which adjuvant therapy to use for colon cancer is determined mainly on the basis of the patient’s TNM stage. Patients with stage III cancers are most commonly considered candidates for a fluoropyrimidine plus oxaliplatin treatment; those with stage II cancers, for a fluoropyrimidine alone or no postsurgical therapy. This standard of care has not changed for more than a decade.1 With the exception of high microsatellite instability (MSI-H) status (which characterizes a subgroup of 15% to 20% of patients with stage II disease who have excellent prognosis and thus no need for adjuvant therapy2), no molecular markers or marker signatures have made relevant inroads into clinical practice. Commercial tests using a limited gene-expression profile analysis are currently being marketed as decision tools for the use of adjuvant therapy in patients with stage II colon cancer, but since these tests have shown only prognostic and not predictive value, their utility in clinical practice is limited.3 This is in contrast to the situation in metastatic colorectal cancer, for which biomarkers are increasingly being used to guide treatment decisions in clinical practice. Activating mutations in exons 2, 3, and 4 of KRAS and NRAS genes have been established as negative predictive markers for the activity of anti–epidermal growth factor receptors such as cetuximab and panitumumab.4 Patients whose tumors show BRAF V600E mutations are known to have a very poor prognosis, and intensified chemotherapy regimens as well as combinations of targeted agents are being developed for this specific population.57 Hypermutated MSI-H cancers have been identified as targets for immune therapy with anti–PD-1/PD-L1 (programmed cell death 1/programmed cell death 1 ligand 1) agents, and human epithelial growth factor receptor 2 (HER2)-positive colorectal cancers appear to respond to HER2-targeted combination therapy.8 These markers, however, characterize only about 15% to 20% of patients with advanced colorectal cancer, and importantly, they represent only single molecular alterations, which are conceivably not an adequate reflection of the complex biology of a cancer cell.

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