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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

Forest plots of hazard ratios comparing overall survival of EGFRis with chemotherapy versus BEV with chemotherapy.
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pone.0140187.g004: Forest plots of hazard ratios comparing overall survival of EGFRis with chemotherapy versus BEV with chemotherapy.

Mentions: Pairwise comparisons of trials examining the efficacy of the same antibody therapy were made first using a random-effects model. Direct pairwise meta-analyses comparing EGFRis versus BEV with chemotherapy in both arms did not detect a difference between the two arms with respect to PFS, HR = 1.02 (CI: 0.93–1.13). However, with respect to OS, a statistically significant difference was seen in favor of the EGFRis arm, HR = 0.79 (CI: 0.65–0.98). The results of PFS and OS comparisons are shown in Figs 3 and 4, respectively. Forest plots of the hazard ratios for PFS and OS between EGFRis vs. chemotherapy alone, and between BEV and chemotherapy alone are available (S4 and S5 Figs, respectively).


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)

Forest plots of hazard ratios comparing overall survival of EGFRis with chemotherapy versus BEV with chemotherapy.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140187.g004: Forest plots of hazard ratios comparing overall survival of EGFRis with chemotherapy versus BEV with chemotherapy.
Mentions: Pairwise comparisons of trials examining the efficacy of the same antibody therapy were made first using a random-effects model. Direct pairwise meta-analyses comparing EGFRis versus BEV with chemotherapy in both arms did not detect a difference between the two arms with respect to PFS, HR = 1.02 (CI: 0.93–1.13). However, with respect to OS, a statistically significant difference was seen in favor of the EGFRis arm, HR = 0.79 (CI: 0.65–0.98). The results of PFS and OS comparisons are shown in Figs 3 and 4, respectively. Forest plots of the hazard ratios for PFS and OS between EGFRis vs. chemotherapy alone, and between BEV and chemotherapy alone are available (S4 and S5 Figs, respectively).

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