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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 showing hazard ratios calculated from direct, indirect and combined analysis of EGFRis versus BEV regimens.For direct comparisons a CI was calculated, and for indirect and combined comparisons, a CR was calculated.
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pone.0140187.g005: Forest plots showing hazard ratios calculated from direct, indirect and combined analysis of EGFRis versus BEV regimens.For direct comparisons a CI was calculated, and for indirect and combined comparisons, a CR was calculated.

Mentions: Indirect comparisons of EGFRis versus BEV (through the intermediate of chemotherapy only: 6 RCTs comparing EGFRis and chemotherapy versus chemotherapy only, 8 RCTs comparing BEV and chemotherapy vs. chemotherapy alone) showed that PFS HR = 1.26 (95% CR: 0.93–1.75) and OS HR = 1.05 (95% CR: 0.81–1.35). Combining the direct and indirect comparisons (17 RCTs) showed a PFS HR = 1.11 (95% CR: 0.92–1.36) in favor of BEV therapy, while OS was in favor of EGFRi therapy, HR = 0.91 (95% CR: 0.75–1.09), although neither result was statistically significant. Fig 5 shows the results of direct pairwise meta-analysis, indirect comparison, and combined analysis for the comparison of EGFRis with BEV. A summary of these results has been provided (S6 Fig). Fig 6 shows a comparison of HRs for combined comparison of: trials prior to FIRE-3, trials up to and including FIRE-3, all trials up to an including CALGB 80405, and all trials excluding FIRE-3. The successive inclusions of FIRE-3 and CALGB trials over time did not change the results that neither EGFRis nor BEV was superior to the other statistically, with increasing precisions with more trials included.


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 showing hazard ratios calculated from direct, indirect and combined analysis of EGFRis versus BEV regimens.For direct comparisons a CI was calculated, and for indirect and combined comparisons, a CR was calculated.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140187.g005: Forest plots showing hazard ratios calculated from direct, indirect and combined analysis of EGFRis versus BEV regimens.For direct comparisons a CI was calculated, and for indirect and combined comparisons, a CR was calculated.
Mentions: Indirect comparisons of EGFRis versus BEV (through the intermediate of chemotherapy only: 6 RCTs comparing EGFRis and chemotherapy versus chemotherapy only, 8 RCTs comparing BEV and chemotherapy vs. chemotherapy alone) showed that PFS HR = 1.26 (95% CR: 0.93–1.75) and OS HR = 1.05 (95% CR: 0.81–1.35). Combining the direct and indirect comparisons (17 RCTs) showed a PFS HR = 1.11 (95% CR: 0.92–1.36) in favor of BEV therapy, while OS was in favor of EGFRi therapy, HR = 0.91 (95% CR: 0.75–1.09), although neither result was statistically significant. Fig 5 shows the results of direct pairwise meta-analysis, indirect comparison, and combined analysis for the comparison of EGFRis with BEV. A summary of these results has been provided (S6 Fig). Fig 6 shows a comparison of HRs for combined comparison of: trials prior to FIRE-3, trials up to and including FIRE-3, all trials up to an including CALGB 80405, and all trials excluding FIRE-3. The successive inclusions of FIRE-3 and CALGB trials over time did not change the results that neither EGFRis nor BEV was superior to the other statistically, with increasing precisions with more trials included.

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