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A Systematic Review and Network Meta-Analysis of Biologic Agents in the First Line Setting for Advanced Colorectal Cancer.

Kumachev A, Yan M, Berry S, Ko YJ, Martinez MC, Shah K, Chan KK - PLoS ONE (2015)

Bottom Line: Seventeen RCTs contained extractable data for quantitative analysis.Combining direct and indirect data using an NMA did not show a statistical difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92-1.36) and OS HR = 0.91 (95% CR: 0.75-1.09)).Direct meta-analysis (3 RCTs), indirect (14 RCTs) and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a difference between EGFRis and BEV.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, University of Toronto, Toronto Canada.

ABSTRACT

Background: Epithelial growth factor receptor inhibitors (EGFRis) and bevacizumab (BEV) are used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). However, few randomized controlled trials (RCTs) have directly compared their relative efficacy on progression-free survival (PFS) and overall survival (OS).

Methods: We conducted a systematic review of first-line RCTs comparing (1) EGFRis vs. BEV, with chemotherapy in both arms (2) EGFRis + chemotherapy vs. chemotherapy alone, or (3) BEV + chemotherapy vs. chemotherapy alone, using Cochrane methodology. Data on and PFS and OS were extracted using the Parmar method. Pairwise meta-analyses and Bayesian network meta-analyses (NMA) were conducted to estimate the direct, indirect and combined PFS and OS hazard ratios (HRs) comparing EGFRis to BEV.

Results: Seventeen RCTs contained extractable data for quantitative analysis. Combining direct and indirect data using an NMA did not show a statistical difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92-1.36) and OS HR = 0.91 (95% CR: 0.75-1.09)). Direct meta-analysis (3 RCTs), indirect (14 RCTs) and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a difference between EGFRis and BEV. Meta-analysis of OS using direct evidence, largely influenced by one trial, showed an improvement with EGFRis therapy (HR = 0.79 (95% CR: 0.65-0.98)), while indirect and combined NMA of OS did not show a difference between EGFRis and BEV Successive inclusions of trials over time in the combined NMA did not show superiority of EGFRis over BEV.

Conclusions: Our findings did not support OS or PFS benefits of EGFRis over BEV in first-line mCRC.

No MeSH data available.


Related in: MedlinePlus

Network of treatment comparisons.The numbers represent the number of studies providing the comparison between the treatment regimens. The solid and dashed lines represent direct and indirect treatment comparisons of studies included in our analysis, respectively.
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pone.0140187.g002: Network of treatment comparisons.The numbers represent the number of studies providing the comparison between the treatment regimens. The solid and dashed lines represent direct and indirect treatment comparisons of studies included in our analysis, respectively.

Mentions: Our electronic search of Medline, Embase and the Cochrane Central Register of Controlled Trials databases yielded 2435 potentially relevant articles. Our manual search through the 2013 and 2014 ASCO General Meeting abstracts produced an additional 62 results. Following a deletion of duplicate results from different databases, there were 1581 records. Ultimately, we identified 17 unique studies for inclusion in the meta-analysis, including 2 ASCO abstracts (Fig 1). Fig 2 shows the network of available treatment comparisons, along with the number of times each comparison was made in a study.


A Systematic Review and Network Meta-Analysis of Biologic Agents in the First Line Setting for Advanced Colorectal Cancer.

Kumachev A, Yan M, Berry S, Ko YJ, Martinez MC, Shah K, Chan KK - PLoS ONE (2015)

Network of treatment comparisons.The numbers represent the number of studies providing the comparison between the treatment regimens. The solid and dashed lines represent direct and indirect treatment comparisons of studies included in our analysis, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608731&req=5

pone.0140187.g002: Network of treatment comparisons.The numbers represent the number of studies providing the comparison between the treatment regimens. The solid and dashed lines represent direct and indirect treatment comparisons of studies included in our analysis, respectively.
Mentions: Our electronic search of Medline, Embase and the Cochrane Central Register of Controlled Trials databases yielded 2435 potentially relevant articles. Our manual search through the 2013 and 2014 ASCO General Meeting abstracts produced an additional 62 results. Following a deletion of duplicate results from different databases, there were 1581 records. Ultimately, we identified 17 unique studies for inclusion in the meta-analysis, including 2 ASCO abstracts (Fig 1). Fig 2 shows the network of available treatment comparisons, along with the number of times each comparison was made in a study.

Bottom Line: Seventeen RCTs contained extractable data for quantitative analysis.Combining direct and indirect data using an NMA did not show a statistical difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92-1.36) and OS HR = 0.91 (95% CR: 0.75-1.09)).Direct meta-analysis (3 RCTs), indirect (14 RCTs) and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a difference between EGFRis and BEV.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, University of Toronto, Toronto Canada.

ABSTRACT

Background: Epithelial growth factor receptor inhibitors (EGFRis) and bevacizumab (BEV) are used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). However, few randomized controlled trials (RCTs) have directly compared their relative efficacy on progression-free survival (PFS) and overall survival (OS).

Methods: We conducted a systematic review of first-line RCTs comparing (1) EGFRis vs. BEV, with chemotherapy in both arms (2) EGFRis + chemotherapy vs. chemotherapy alone, or (3) BEV + chemotherapy vs. chemotherapy alone, using Cochrane methodology. Data on and PFS and OS were extracted using the Parmar method. Pairwise meta-analyses and Bayesian network meta-analyses (NMA) were conducted to estimate the direct, indirect and combined PFS and OS hazard ratios (HRs) comparing EGFRis to BEV.

Results: Seventeen RCTs contained extractable data for quantitative analysis. Combining direct and indirect data using an NMA did not show a statistical difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92-1.36) and OS HR = 0.91 (95% CR: 0.75-1.09)). Direct meta-analysis (3 RCTs), indirect (14 RCTs) and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a difference between EGFRis and BEV. Meta-analysis of OS using direct evidence, largely influenced by one trial, showed an improvement with EGFRis therapy (HR = 0.79 (95% CR: 0.65-0.98)), while indirect and combined NMA of OS did not show a difference between EGFRis and BEV Successive inclusions of trials over time in the combined NMA did not show superiority of EGFRis over BEV.

Conclusions: Our findings did not support OS or PFS benefits of EGFRis over BEV in first-line mCRC.

No MeSH data available.


Related in: MedlinePlus