The efficacy and safety of adding bevacizumab to cetuximab- or panitumumab-based therapy in the treatment of patients with metastatic colorectal cancer (mCRC): a meta-analysis from randomized control trials

Abstract

Objective: To estimate the efficacy and safety of adding bevacizumab to cetuximab- or panitumumab-based therapy in the treatment of patients with metastatic colorectal cancer (mCRC), using a meta-analysis of randomized controlled trials.

Methods: A literature search for randomized clinical trials (RCTs) was performed through Pubmed, Embase, and Web of Science (up to May 22, 2014). The outcome measures were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events. Two investigators identified eligible studies and extracted data independently. The quality of the included studies was assessed by the Jadad score. Hazard ratios (HR), risk ratio (RR), and 95% confidence intervals (Cls) were calculated and pooled.

Results: A total of 4 RCTs with 2069 patients were included in this meta-analysis. The addition of bevacizumab to cetuximab- or panitumumab-based therapy did not significantly prolonged PFS, when compared with antibody alone. The subgroup analysis of adding bevacizumab to cetuximab-based therapy also suggested no significant benefit in PFS or in OS. Patients who received the combined therapy did not have a higher ORR (RR = 0.98, 95% CI: 0.89-1.07; P = 0.608). The incidence of grade 3/4 adverse events was not significantly higher in the bevacizumab and cetuximab/panitumumab group.

Conclusion: The addition of bevacizumab to cetuximab- or panitumumab-based therapy did not improve PFS and OS resulting in better ORR. Thus, the combined therapy of bevacizumab with cetuximab or panitumumab is not recommended for the treatment of mCRC. However, larger scale RCTs are needed to confirm these findings.

Keywords: EGFR; Olorectal cancer; VEGF; bevacizumab; cetuximab; meta-analysis; panitumumab.

Figure 1

Eligibility of studies for inclusion in meta-analysis (Abbreviations: Bev, bevacizumab; Cet, cetuximab).

Figure 2

Meta-analysis exploring the effect of addition of bevacizumab to cetuximab- or panitumumab-based therapy on progression-free survival (PFS) and overall survival (OS).

Figure 3

Test for publication bias for HR of progression-free survival (PFS).

Figure 4

Meta-analysis exploring the effect of addition of bevacizumab to cetuximab- or panitumumab-based therapy on objective response rate (ORR).

Figure 5

Meta-analysis exploring the risk ratio of Grade 3/4 adverse events in patients with addition of bevacizumab to cetuximab- or panitumumab-based therapy versus antibody alone.