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

Oncotarget. 2017 Jul 5;8(32):53631-53641. doi: 10.18632/oncotarget.19022. eCollection 2017 Aug 8.

Abstract

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.

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