Abstract

BackgroundA first-line biologic treatment for metastatic colorectal cancer (mCRC) is still controversial. We, therefore, performed a meta-analysis to determine the efficacy of first-line cetuximab versus bevacizumab for RAS and BRAF wild-type mCRC.MethodsIn March 2018, an electronic search of the following biomedical databases was performed: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov and Web of Knowledge. Randomized controlled trials (RCTs) and prospective or observational cohort studies (OCSs) were included. Subgroup analyses of all RCTs were performed in all outcomes. All statistical analyses were performed using RevMan software 5.3.ResultsTwo RCTs and three OCSs, involving a total 2576 patients, were included. The meta-analysis reported that cetuximab was associated with a longer overall survival (OS) [HR 0.89, 95% CI (0.81–0.98); p = 0.02], a higher ORR [RR 1.11, 95% CI (1.03–1.19); p = 0.006], higher complete response [RR 3.21, 95% CI (1.27–8.12); p = 0.01] and a greater median depth of response than bevacizumab. However, no significant difference was observed between cetuximab and bevacizumab groups for PFS, DCR, partial response, progressive disease, curative intent metastasectomy, EORR and incidence of grade 3 or higher adverse events. In the subgroup meta-analyses of the RCTs, inconsistent results compared to the main analysis, however, were found, in the ORR, DCR and curative intent metastasectomy.ConclusionsThe current evidence indicates that compared to bevacizumab treatment, cetuximab provides a clinically relevant effect in first-line treatment against mCRC, at the cost of having lower stable disease.

Highlights

  • A first-line biologic treatment for metastatic colorectal cancer is still controversial

  • No significant difference was observed between cetuximab and bevacizumab groups for progression-free survival (PFS), disease control rate (DCR), partial response, progressive disease, curative intent metastasectomy, Early objective response rate (EORR) and incidence of grade 3 or higher adverse events

  • In the subgroup meta-analyses of the Randomized controlled trials (RCTs), inconsistent results compared to the main analysis, were found, in the objective response rate (ORR), DCR and curative intent metastasectomy

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Summary

Introduction

A first-line biologic treatment for metastatic colorectal cancer (mCRC) is still controversial. We performed a meta-analysis to determine the efficacy of first-line cetuximab versus bevacizumab for RAS and BRAF wild-type mCRC. Colorectal cancer (CRC) is the third most common cause of cancer-related morbidity worldwide [1], with a 14% five-year survival rate in patients with an initial diagnosis of metastatic colorectal cancer (mCRC) [2]. With the increasing use of targeted therapies, including epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF) antibody, the median overall survival (OS) of mCRC has been raised to approximately 30 months over the last 10 years [5, 6]. Studies several trials have shown clinical efficacy of cetuximab in KRAS wild-type mCRC [10, 11]

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