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

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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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Author notes

    Authors and Affiliations

    1. Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, People’s Republic of China

      Wei Xu, Yang Gong, Peng Wu, Jinfei Chen & Cuiju Tang

    2. Department of Oncology, Liyang People’s Hospital, Liyang, Jiangsu, People’s Republic of China

      Meng Kuang

    3. Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China

      Chunxiang Cao

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    1. Wei Xu
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    2. Yang Gong
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    3. Meng Kuang
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    4. Peng Wu
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    Correspondence to Jinfei Chen or Cuiju Tang.

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    Funding

    This study was supported by a grant from The Project of Plans for the Development of Science and Technology of Nanjing, China (Grant No. 201208020).

    Conflict of interest

    Wei Xu, Yang Gong, Meng Kuang, Peng Wu, Chunxiang Cao, Jinfei Chen, and Cuiju Tang declare no conflicts of interest.

    Additional information

    W. Xu and Y. Gong contributed equally to this work and share first authorship.

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    Xu, W., Gong, Y., Kuang, M. et al. Survival Benefit and Safety of Bevacizumab in Combination with Erlotinib as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: A Meta-Analysis. Clin Drug Investig 37, 155–165 (2017). https://doi.org/10.1007/s40261-016-0465-0

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    • DOI: https://doi.org/10.1007/s40261-016-0465-0

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