The impact of primary tumor location on efficacy of cetuximab in metastatic colorectal cancer patients with different Kras status: a systematic review and meta-analysis

De-Dong Cao, Hui-Lin Xu, Xi-Ming Xu and Wei Ge _

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Oncotarget. 2017; 8:53631-53641. https://doi.org/10.18632/oncotarget.19022

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De-Dong Cao1, Hui-Lin Xu2, Xi-Ming Xu1 and Wei Ge1

1Department of Oncology, RenMin Hospital of Wuhan University, Wuhan, China

2Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, China

Correspondence to:

Wei Ge, email: gewei514@126.com

Xi-Ming Xu, email: doctorxu120@aliyun.com

Keywords: primary tumor location, cetuximab, colorectal cancer, Kras, meta-analysis

Received: August 10, 2016     Accepted: June 20, 2017     Published: July 05, 2017


Objective: To assess the prognostic role of primary tumor location along with Kras status in metastatic colorectal cancer (mCRCs) treated with cetuximab.

Materials and Methods: Databases of EMBASE, Pubmed, the Cochrane library, China National Knowledge Infrastructure and other databases from inception to July 2016 were searched. Randomized controlled trial (RCT) and/or retrospective studies of influence of primary tumor location on efficacy of cetuximab in patients with mCRC were identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), overall response rate (ORR) and disease control rate (DCR).

Results: Ten studies including 2977 cases were finally included. The results of meta-analysis were in favor of cetuximab to patients with left-sided colorectal cancer in terms of OS (HR = 0.52, 95% CI: 0.40–0.66; p < 0.01), PFS (HR = 0.64, 95% CI: 0.58–0.70; p < 0.01), and ORR (OR = 2.17, 95% CI: 1.57–2.99; p < 0.01). Patients with right-sided CRC gained less benefit from cetuximab in terms of OS (HR = 1.89, 95% CI: 1.43–2.50; p < 0.01), compared with left-sided CRC. Regarding Kras status, left-sided mCRC with wild type Kras had better PFS (HR = 0.61, 95% CI: 0.51–0.74; p < 0.01) and OS (HR = 0.49, 95% CI: 0.35–0.69; p < 0.01) than right-sided cases when treated with cetuximab. We also found that cetuximab was both significantly effective in different treatment lines and regions when comparing by primary tumor locations (p < 0.01).

Conclusions: mCRC Patients with left-sided, wild type Kras have a better prognosis than those with right-sided diseases when treated with cetuximab. The clinical application of cetuximab should be determined by the primary tumor location and molecular gene mutation status.

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