The Impact of Microsatellite Instability Status and Sidedness of the Primary Tumor on the Effect of Cetuximab-Containing Chemotherapy in Patients with Metastatic Colorectal Cancer

Background: Colorectal cancer (CRC) has been reconsidered as a heterogeneous disease. Among advances of genomic analysis in CRC, the sidedness of tumors (left-sided colon vs. right-sided colon) and microsatellite instability (MSI)-high (H) tumors have been highlighted. Methods: We analyzed 153 CRC patients who were available for evaluation of MSI status and had been treated with cetuximab-containing chemotherapy between April 2008 and January 2013. KRAS mutational status was available in all 153 patients, but BRAF mutational status was only available in 72 patients (47.1%). We evaluated the impact of microsatellite instability status and location of the primary colon tumor on the effect of cetuximab-containing chemotherapy in patients with metastatic colorectal cancer. Results: MSI-H was detected in 3.9% of analyzed patients. Characteristics of patients, with the exception of BRAF mutational status, were generally similar between those with right and left-sided tumors. Right-sided tumors were significantly associated with a BRAF mutation (p=0.023). In addition, patient characteristics with an MSS tumor were not different from those with an MSI-H tumor. For all 153 patients, the most commonly used regimen that included cetuximab was irinotecan alone, irrespective of treatment line. There was no significant difference in treatment efficacy in either RR or disease control rate (DCR) between the MSI-H and MSS groups. There was also no difference in RR and DCR according to the location of the primary tumor (left side vs. right side). No significant difference in PFS was observed between the MSI-H and MSS groups (4.80 months vs. 5.80 months; p=0.238) or the left-side and right-side groups (6.10 months vs. 4.20 months; p=0.278). In a subgroup-analysis of 140 patients with wild-type KRAS, there was no difference in PFS following cetuximab-containing therapy based on MSI status or the location of the primary tumor. Conclusions: MSI status and the location of the primary tumor were not novel biomarkers for response to cetuximab-containing therapy in metastatic CRC. Further prospective validation of the prognostic or predictive capacity of MSI status and the sidedness of tumors is warranted.