Impact of Primary Tumor Localization on the Efficacy of Bevacizumab in Metastatic Colorectal Cancer

Aim: Right-and left-sided primary tumors of colorectal origin differ substantially in several aspects. Recent retrospective analyses show distinct efficacy of EGFR-epidermal growth factor receptor (EGFR)-directed therapies for left-and right-sided primary tumors. Current treatment guidelines have accommodated these findings such that for right-sided primary tumors, EGFR-directed therapy is no longer recommended. Instead, vascular endothelial growth factor (VEGF)-directed therapies are recommended frequently in first line, even in tumors with wild-type rat sarcoma (RAS) status. However, data supporting this recommendation are scarce. The purpose of this analysis was to investigate the efficacy of bevacizumab added to chemotherapy depending on the primary tumor localization in a retrospective setting. Patients and Methods: From the central clinical cancer registry of one of Germany's largest medical centers, data were analyzed for patients with metastatic colorectal cancer (mCRC) treated with either chemotherapy alone (CT) or bevacizumab-containing regimens (BEV/CT). Results: Of 1,080 documented mCRC cases within the period of 2003 through 2016, 242 were treated with chemotherapy alone and 166 with bevacizumab-containing regimes in any line of therapy meeting the criterion above. In patients with left-sided primary tumor localization, a significant survival benefit was found when bevacizumab was added to chemotherapy. Patients with right-sided primaries, instead, did not derive any advantage when bevacizumab was added to chemotherapy. For the whole group of patients, this translated into a trend towards improved survival in bevacizumab-treated patients with mCRC. Conclusion: Adding bevacizumab to chemotherapy in mCRC may be beneficial only in patients with left-sided primary tumor, while those with right-sided primary tumors may have no additional benefit from the addition of bevacizumab. This hypothesis-generating analysis should provide a basis for in-depth analysis of this issue in future prospective trials.