Abstract
BackgroundColorectal 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.ResultsFifteen 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 MethodsLiterature 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.ConclusionsFurther 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.
Highlights
Colorectal cancer is a relatively common and deadly cancer, accounting for around 10% of both incident cancers and cancer mortalities in both women and men globally [1].Risk factors can be non-modifiable, including age, a personal or family history of adenomatous polyps, and inflammatory bowel diseases, or modifiable, including diet, physical inactivity, obesity, smoking, and alcohol [2]
There was a lack of decisive evidence that FOLFIRI or FOLFOX impact efficacy of either anti-epidermal growth factor receptor (EGFR) or antiVEGF, across mutational status groups
Evidence suggests that both anti-EGFR and anti-vascular endothelial growth factor (VEGF) therapies, when combined with FOLFIRI or FOLFOX, may be harmful as compared to chemotherapy for KRAS MT patients
Summary
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 antiVEGF, across mutational status groups. 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. 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
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