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

Oncotarget 2017 September 13
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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