Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer

Background: The relationship of epidermal growth factor receptors (EGFR) pathway, such as PI3K, K-ras, and B-raf, with response to EGFR-targeted antibodies is less well studied. Aim: To assess sorafenib with cetuximab in treating metastatic colorectal cancer. Settings and Design: Thirty-five patients with metastatic colorectal cancer were randomized to receive cetuximab with or without oral sorafenib. Patients and Methods: Patients received cetuximab IV weekly for four weeks and oral sorafenib twice daily on days 1 - 28, with recycling every four weeks. The primary end point was the response rate (partial and complete), while the secondary end points were the adverse effects, time to progression and overall survival. Statistical Analysis was made using the Statistical Product and Service Solutions, using SPSS 10.0, with estimation of both time to progression and overall survival time by the Kaplan-Meier method and comparing the two groups with the use of a log-rank test. Results: Partial response was higher in cetuximab-sorafenib (EN), which constituted 33.3% compared to 17.6% in the cetuximab group (P = 0.44). Progression-free survival had a statistically higher significant difference in wild K-ras compared to mutant K-ras cases (P = .0001). Median overall survival was seven and five months in the (EN) and (E) groups respectively (P = 0.49). Conclusion: K-ras and B-raf was a predictor of response, so genotyping of tumors was needed for defining the patient population that was likely to benefit from the targeted therapy. A combination of therapy that simultaneously targets K-ras and B-raf could be a useful approach to increase the number of patients who may benefit from anti-EGFR therapy.