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Anti-EGFR antibody versus anti-VEGF antibody with first-line chemotherapy
Source: Rectal Cancer Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: February 12, 2025 · Captured 2026-09-09.
Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary. Independent clinical review is pending.
In the management of patients with stage IV colorectal cancer, it is unknown whether patients with KRAS wild-type cancer should receive an anti-EGFR antibody with chemotherapy or an anti-VEGF antibody with chemotherapy. Two studies attempted to answer this question.[46,47]
Evidence (anti-EGFR antibody vs. anti-VEGF antibody with first-line chemotherapy):
The FIRE-3 study (NCT00433927) randomly assigned 592 patients with KRAS exon 2 wild-type tumors who were previously untreated to FOLFIRI plus cetuximab (297 patients) or FOLFIRI plus bevacizumab (295 patients). The primary end point of the study was objective response rate.[46][Level of evidence A1]
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The FIRE-3 study (NCT00433927) randomly assigned 592 patients with KRAS exon 2 wild-type tumors who were previously untreated to FOLFIRI plus cetuximab (297 patients) or FOLFIRI plus bevacizumab (295 patients). The primary end point of the study was objective response rate.[46][Level of evidence A1]
The objective response rate was not significantly different between the groups (objective response rate, 62.0%; 95% CI, 56.2–67.5 vs. objective response rate, 58.0%; 95% CI, 52.1–63.7; odds ratio, 1.18; 95% CI, 0.85–1.64; P = .18).
The FIRE-3 study (NCT00433927) randomly assigned 592 patients with KRAS exon 2 wild-type tumors who were previously untreated to FOLFIRI plus cetuximab (297 patients) or FOLFIRI plus bevacizumab (295 patients). The primary end point of the study was objective response rate.[46][Level of evidence A1]
Median PFS was 10.0 months (95% CI, 8.8–10.8) in the cetuximab group and 10.3 months (95% CI, 9.8–11.3) in the bevacizumab group (HR, 1.06; 95% CI, 0.88–1.26; P = .55).
The FIRE-3 study (NCT00433927) randomly assigned 592 patients with KRAS exon 2 wild-type tumors who were previously untreated to FOLFIRI plus cetuximab (297 patients) or FOLFIRI plus bevacizumab (295 patients). The primary end point of the study was objective response rate.[46][Level of evidence A1]
Median OS was 28.7 months (95% CI, 24.0–36.6) in the cetuximab group compared with 25.0 months (range, 22.7–27.6 months) in the bevacizumab group (HR, 0.77; 95% CI, 0.62–0.96; P = .017).
The FIRE-3 study (NCT00433927) randomly assigned 592 patients with KRAS exon 2 wild-type tumors who were previously untreated to FOLFIRI plus cetuximab (297 patients) or FOLFIRI plus bevacizumab (295 patients). The primary end point of the study was objective response rate.[46][Level of evidence A1]
In a post hoc analysis of patients with expanded RAS wild-type tumors (sequencing for mutational hot spots within KRAS and NRAS genes, including exon 2 codons 12 and 13; exon 3 codons 59 and 61; and exon 4 codons 117 and 146), the median OS was 33.1 months (95% CI, 24.5–39.4) in the cetuximab group compared with 25.0 months (95% CI, 23.0–28.1) in the bevacizumab group (HR, 0.70; 95% CI, 0.54–0.90; P = .0059).[48]
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The FIRE-3 study (NCT00433927) randomly assigned 592 patients with KRAS exon 2 wild-type tumors who were previously untreated to FOLFIRI plus cetuximab (297 patients) or FOLFIRI plus bevacizumab (295 patients). The primary end point of the study was objective response rate.[46][Level of evidence A1]
Of note, only 52% of patients assigned to the bevacizumab arm subsequently received cetuximab or panitumumab.[49]
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The Cancer and Leukemia Group B Intergroup study 80405 (NCT00265850) was presented at the American Society of Clinical Oncology meeting in 2014. This study randomly assigned 2,334 previously untreated patients with KRAS wild-type cancer to chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or chemotherapy plus cetuximab. OS was the primary end point.[47][Level of evidence B1]
Source links and citations
The Cancer and Leukemia Group B Intergroup study 80405 (NCT00265850) was presented at the American Society of Clinical Oncology meeting in 2014. This study randomly assigned 2,334 previously untreated patients with KRAS wild-type cancer to chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or chemotherapy plus cetuximab. OS was the primary end point.[47][Level of evidence B1]
There was no statistically significant difference in OS among the patients assigned to bevacizumab or cetuximab (for OS differences, chemotherapy/bevacizumab = 29.04 months [range, 25.66–31.21 months] vs. chemotherapy/cetuximab = 29.93 months [range, 27.56–31.21 months]; HR, 0.92 [0.78–1.09]; P = .34).
Based on these two studies, no apparent significant difference is evident about starting treatment with chemotherapy/bevacizumab or chemotherapy/cetuximab in patients with KRAS wild-type metastatic colorectal cancer. However, in patients with KRAS wild-type cancer, administration of an anti-EGFR antibody at some point during management improves OS.
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Preserved source evidence · Independent clinical review pending · Not medical advice