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

Abstract

BackgroundThe 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.ObjectiveThe aim was to investigate the comparative effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens and compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC, through an updated systematic review and meta-analysis of concurrent or non-concurrent observational cohort studies, to guide authorities and the judiciary.MethodA systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures included OS, PFS, post-progression survival (PPS), Response Evaluation Criteria In Solid Tumors (RECIST), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated.ResultsA total of 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (10.1007/s40259-018-0322-1) contains supplementary material, which is available to authorized users.

Review of Ongoing Activities and Challenges to Improve the Care of Patients With Type 2 Diabetes Across Africa and the Implications for the Future

“…Consequently, countries can learn from each other. We also did not systematically review each paper for its quality using well-known scales such as the Newcastle-Ottawa scale or the Cochrane risk of bias tool as our emphasis was on contextualizing the findings rather than performing a systematic review for the reasons given (Marra et al, 2016;Ong et al, 2018;Almeida et al, 2018;da Silva et al, 2018;Saleem et al, 2019). In addition, we did not review each paper to assess whether the presence of diabetes, especially T2DM, had been defined according to WHO and other internationally recognized diagnostic criteria in view of the objectives of this paper (World Health Organisation, 2006;Manne-Goehler et al, 2019).…”

EGFL6 Promotes Colorectal Cancer Cell Growth and Mobility and the Anti-cancer Property of Anti-EGFL6 Antibody

“…The current CRC rst-line treatment is bevacizumab combined with chemotherapy, such as 5-FU, oxaliplatin or irinotecan, the regimens evidently improve overall and progression-free survival in CRC patients. However, it worth to noted that in a meta-analysis review article, there are some statistically signi cant increase in severe adverse events associated with bevacizumab, for example, severe hypertension and gastrointestinal perforation [28]. In addition, Koichi Taira et al reported that patient received bevacizumab occurred skin ulcer and wound healing delayed, recommended the treatment of bevacizumab should be suspended at least 5 weeks before patient undergo an operation [29].…”

EGFL6 promotes colorectal cancer cell growth and mobility and the anti-cancer property of anti-EGFL6 antibody

“…The current CRC rst-line treatment is bevacizumab combined with chemotherapy, such as 5-FU, oxaliplatin or irinotecan, the regimens evidently improve overall and progression-free survival in CRC patients. However, it worth to noted that in a meta-analysis review article, there are some statistically signi cant increase in severe adverse events associated with bevacizumab, for example, severe hypertension and gastrointestinal perforation [25]. In addition, Koichi Taira et al reported that patient received bevacizumab occurred skin ulcer and wound healing delayed, recommended the treatment of bevacizumab should be suspended at least 5 weeks before patient undergo an operation [26].…”