The role of targeted agents in the adjuvant treatment of colon cancer: a meta-analysis of randomized phase III studies and review

There has been debate as to whether targeted agents have beneficial effect when added to adjuvant chemotherapy for patient with colon cancer. We conducted this meta-analysis to investigate the role of targeted agents in the adjuvant treatment of colon cancer. We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library databases. We included phase III trials with the data of disease-free survival (DFS) and adverse events (AEs) of adjuvant treatment with targeted agents. From 5 eligible studies, a total of 9,991 patients with resected colon cancer were included in the meta-analysis of hazard ratio (HR) for 3-year DFS and odds ratio (OR) for grade 3 or higher AEs. The addition of targeted agents showed no improvement of 3-year DFS, compared to standard adjuvant chemotherapy alone (HR = 1.04 [95% confidence interval (CI), 0.96-1.13], P = 0.31). In the subgroup analysis according to the type of targeted agents, neither bevacizumab (HR = 1.03 [95% CI, 0.88-1.21], P = 0.72) nor cetuximab (HR = 1.11 [95% CI, 0.94-1.31], P = 0.22) was associated with improvement of DFS. Moreover, targeted agents significantly increased grade 3 or higher AEs (OR = 1.73 [95% CI, 1.21-2.46], P = 0.003) and treatment-related death (OR = 2.15 [95% CI, 1.16-3.99], P = 0.02). In conclusion, this meta-analysis demonstrates that the addition of targeted agents to standard adjuvant chemotherapy results in no improvement of DFS with increased severe AEs and treatment-related death in patients with resected colon cancer.