Comparative effectiveness and safety of monoclonal antibodies (Bevacizumab, Cetuximab, and Panitumumab) in combination with chemotherapy for metastatic colorectal cancer : a systematic review and meta-analysis

da Silva, Wânia Cristina and de Araújo, Vânia Eloisa and Lima, Ellias Magalhães Abreu and Dos Santos, Jéssica Barreto Ribeiro and da Silva, Michael Ruberson Ribeiro and Almeida, Paulo and de Assis Acurcio, Francisco and Godman, Brian and Kurdi, Amanj and Cherchiglia, Mariangela Leal and Gurgel Andrade, Eli Iola (2018) Comparative effectiveness and safety of monoclonal antibodies (Bevacizumab, Cetuximab, and Panitumumab) in combination with chemotherapy for metastatic colorectal cancer : a systematic review and meta-analysis. BioDrugs, 32 (6). pp. 585-606. ISSN 1179-190X (

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Background: The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5- Fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed. Objective: To compare the effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens or compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC through an updated systematic review and meta-analysis with concurrent or non concurrent observational cohort studies to guide the authorities and judiciary. Method: A systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures include OS, PFS, post-progression survival (PPS), RECIST (Response Evaluation Criteria In Solid Tumors), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated. Results: 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities, and concerns with the heterogeneity of the studies. Conclusion: The results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation that need to be considered.


da Silva, Wânia Cristina, de Araújo, Vânia Eloisa, Lima, Ellias Magalhães Abreu, Dos Santos, Jéssica Barreto Ribeiro, da Silva, Michael Ruberson Ribeiro, Almeida, Paulo, de Assis Acurcio, Francisco, Godman, Brian, Kurdi, Amanj ORCID logoORCID:, Cherchiglia, Mariangela Leal and Gurgel Andrade, Eli Iola;