Molecular Predictors of Response in Stage III Colon Cancer

Douglas K. Rex, MD

Five-year survival rates were lowest in patients with tumors characterized as having proficient mismatch repair status and either BRAF or KRAS mutations.

Stage III colon cancer (lymph node involvement without distant metastases) is typically treated with adjuvant chemotherapy. Treatment decisions are currently based on tumor stage classification, but further classification of tumors based on molecular biomarkers is sought to improve prognosis determination and guide therapy.

In the current analysis, investigators conducted molecular testing of stage III colorectal tumors in 2720 patients undergoing adjuvant therapy with FOLFOX or FOLFOX plus cetuximab. They classified tumors into five subtypes. Mismatch repair (MMR) status was characterized as proficient (pMMR) or deficient (dMMR). The pMMR tumors were classified as BRAF-mutated (7% of the entire cohort), KRAS-mutated (35%), or lacking mutations in either BRAF or KRAS (49%). The dMMR tumors were classified as BRAF-mutated (7%) or the familial type (3%). Five-year, disease-free survival was higher in patients with pMMR tumors without BRAF or KRAS mutations (71%) compared with those with KRAS mutation (61%) or the BRAF mutation (56%). In patients with dMMR tumors, disease-free survival was similar to that in patients with pMMR tumors with neither BRAF nor KRAS mutations.

Citation(s):

Sinicrope FA et al. Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology 2015 Jan; 148:88.