Abstract
ObjectiveTo assess the prognostic role of primary tumor location along with Kras status in metastatic colorectal cancer (mCRCs) treated with cetuximab.Materials and MethodsDatabases 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).ResultsTen 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).ConclusionsmCRC 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.
Highlights
Colorectal cancer (CRC) is one of the most common malignances worldwide, accounted for 9.7% of all incident cancers in 2015 [1]
The results of meta-analysis were in favor of cetuximab to patients with left-sided colorectal cancer in terms of overall survival (OS) (HR = 0.52, 95% confidence interval (CI): 0.40–0.66; p < 0.01), progression-free survival (PFS) (HR = 0.64, 95% CI: 0.58–0.70; p < 0.01), and overall response rate (ORR) (OR = 2.17, 95% CI: 1.57–2.99; p < 0.01)
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
Summary
Colorectal cancer (CRC) is one of the most common malignances worldwide, accounted for 9.7% of all incident cancers in 2015 [1]. A decline in CRC mortality have been observed in North America, European countries, and Japan [1, 2]. These improvements in reducing CRC caused death are thought to be achieved by adequate prevention, early diagnosis, and effective treatment regimens [3]. With regards to metastatic CRC, the application of molecular targeted therapies, such as cetuximab, is reported to improve clinical outcome in this population [4, 5]. The efficacy of cetuximab is determined by several clinical and molecular characteristics and not all of these metastatic CRC patients are benefited from this agent, indicating that application of cetuximab should be considered according to personalized information [6, 7]. It is necessary to find specific www.impactjournals.com/oncotarget clinical feature and biomarker to identify patients who can gain favorable outcome from cetuximab administration
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