Survival Benefit and Safety of Bevacizumab in Combination with Erlotinib as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: A Meta-Analysis

Abstract

Background

Recently, the need for maintenance chemotherapy arose as a result of the significantly improved survival of patients with metastatic colorectal cancer (mCRC) without increasing adverse events. Currently used maintenance regimens are fluoropyrimidines, bevacizumab, and the combination of fluoropyrimidine with bevacizumab. A new combination with bevacizumab and erlotinib, a tyrosine kinase inhibitor of the epithelial growth factor receptor, has shown synergistic effects in preclinical tests and promising results in some clinical trials. Whether bevacizumab combined with erlotinib vs. bevacizumab alone as maintenance therapy will further improve the clinical outcomes in patients with mCRC is controversial. We conducted this meta-analysis to compare the survival benefit and safety of these two regimens in patients with mCRC.

Methods

We searched PubMed, EMBASE, and the Central Registry of Controlled Trials of the Cochrane Library up to August 2016. We also searched the Proceedings of the American Society of Clinical Oncology (1986 to August 2016). Abstracts were manually searched to identify relevant trials. A total of three randomized controlled trials with 682 patients met the inclusion criteria.

Results

Our results demonstrated that bevacizumab combined with erlotinib significantly improved overall survival (hazard ratio 0.78; 95 % confidence interval 0.66–0.93; p = 0.006) and progression-free survival (hazard ratio 0.79; 95 % confidence interval 0.68–0.92; p = 0.002). Significantly more grade 3 rash, diarrhea, infection total, and fatigue were observed in the bevacizumab combined with erlotinib arm, which were controllable and reversible.

Conclusions

Based on current evidence, the addition of erlotinib to bevacizumab as maintenance therapy significantly increases overall survival and progression-free survival with an increased but manageable toxicity in patients with mCRC. It should be considered as a treatment option for these patients under the premise of a reasonable selection of the target population.

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