Sustainable Clinical Development of Adjuvant Chemotherapy for Colon Cancer

Abstract

Numerous clinical studies in an adjuvant setting have been conducted and the combination therapy of 5-fluorouracil and oxaliplatin has been established as the standard treatment for Stage III and as an option for high-risk Stage II patients. Biologics such as bevacizumab and antiepidermal growth factor receptor antibodies have failed to show additional survival benefits. The indication of adjuvant chemotherapy has been determined according to the pathological stage. Nevertheless, a pathological diagnosis does not necessarily result in selection of the optimal treatment. To improve treatment decisions, many trials have aimed to stratify patients into treatment groups using genomic testing. Recently, gene signature, Immunoscore, and circulating tumor DNA (ctDNA) assays have been reported and among them, ctDNA was shown to be a promising accurate predictive marker for recurrence. Treatment of ctDNA-positive patients with aggressive chemotherapy may reduce recurrence rates. The ultimate goal is to accurately predict the risk of recurrence and to prevent recurrence in colon cancer patients. In this review we focus on the clinical development of adjuvant chemotherapy and stratification of patients according to risk of recurrence and the future direction of adjuvant chemotherapy.

Keywords: BRAF; MSI; RAS; adjuvant chemotherapy; colon cancer; ctDNA.