Targeted first-line therapies for advanced colorectal cancer: a Bayesian meta-analysis

Yassine Ridouane, Gilberto Lopes, Geoffrey Ku, Hasan Masud and Benjamin Haaland _

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Oncotarget. 2017; 8:66458-66466. https://doi.org/10.18632/oncotarget.20185

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Yassine Ridouane1, Gilberto Lopes2, Geoffrey Ku3, Hasan Masud1 and Benjamin Haaland1,4

1H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA, USA

2Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA

3Memorial Sloan Kettering Cancer Center, New York, NY, USA

4Population Health Sciences and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

Correspondence to:

Benjamin Haaland, email: [email protected]

Keywords: Bayesian, colorectal cancer, decision analysis, meta-analysis, targeted therapy

Received: May 10, 2017     Accepted: August 03, 2017     Published: August 11, 2017


Background: Colorectal cancer is common and deadly. First-line treatments for patients with metastatic disease include FOLFIRI and FOLFOX, which have been combined with anti-EGFR or anti-VEGF antibodies to achieve benefit in selected populations. However, optimal therapy remains unclear.

Results: Fifteen publications on 10 trials were identified. There was a lack of decisive evidence that FOLFIRI or FOLFOX impact efficacy of either anti-EGFR or anti-VEGF, across mutational status groups. On the other hand, evidence suggests both anti-EGFR and anti-VEGF may be more effective for KRAS WT than MT patients. KRAS WT results provided evidence that anti-EGFR treatments may be more effective than anti-VEGF treatments when combined with FOLFIRI or FOLFOX. Further, evidence suggests that both anti-EGFR and anti-VEGF therapies, when combined with FOLFIRI or FOLFOX, may be harmful as compared to chemotherapy for KRAS MT patients.

Materials and Methods: Literature was searched for randomized trials comparing anti-EGFR or anti-VEGF antibodies, paired with FOLFIRI or FOLFOX, as first-line therapy for advanced colorectal cancer. Meta-estimates were generated via Bayesian hierarchical log-linear model. The primary endpoint was overall survival.

Conclusions: Further studies examining impact of all-RAS mutation status, left or right side location of primary tumor, and combination anti-VEGF with modern bolus fluoropyrimidine are needed.

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