Cetuximab versus bevacizumab in metastatic colorectal cancer: a comparative effectiveness study

J Cancer Res Clin Oncol. 2020 May;146(5):1321-1334. doi: 10.1007/s00432-020-03167-0. Epub 2020 Mar 6.

Abstract

Purpose: Uncertainty exists regarding comparative effectiveness of cetuximab versus bevacizumab in metastatic colorectal cancer (mCRC). We conducted a retrospective head-to-head multi-cohort study comparing clinical outcomes from both antibodies METHODS: Cohorts were defined by treatment line and subgroups by (K)RAS status and tumour sidedness. Among other outcomes, we estimated and compared response rates, progression-free (PFS) and overall survival (OS).

Results: Between January 2010 and April 2018, 311 patients were included. Except for (K)RAS mutation status, baseline characteristics were balanced across treatment groups. In the full analysis of first and second-line cohorts, PFS (first-line: HR = 0.85; 95% CI 0.64 to 1.13; P = 0.26; second-line: HR = 1.16; 95% CI 0.74 to 1.83; P = 0.51) and OS (first-line: HR = 0.83; 95% CI 0.61 to 1.15; P = 0.26; second-line: HR = 0.88; 95% CI 0.56 to 1.38; P = 0.58) were similar between bevacizumab and cetuximab arms. In subgroup analyses of first-line therapy, we found a survival difference favouring bevacizumab in right-sided tumours (PFS: HR = 0.52; 95% CI 0.29 to 0.93; P = 0.025; OS: HR = 0.60; 95% CI 0.32 to 1.12; P = 0.11), but not in left-sided (HR = 1.04; 95% CI 0.75 to 1.46; P = 0.81; OS: HR = 0.94; 95% CI 0.65 to 1.36; P = 0.74), or (K)RAS wild-type tumours (PFS: HR = 0.91; 95% CI 0.60 to 1.40; P = 0.67; OS: HR = 0.79; 95% CI 0.50 to 1.25; P = 0.31). Response rates were similar across treatment groups, except for the subgroup of patients bearing right-sided primaries, where bevacizumab performed substantially better.

Conclusion: This study provides evidence suggesting bevacizumab and cetuximab lead to similar effectiveness outcomes in mCRC, except for right-sided tumours, where cetuximab seemed to show considerably poorer outcomes. Further research is needed to confirm these results.

Keywords: Bevacizumab; Cetuximab; Colorectal cancer; Comparative effectiveness research; Tumour sidedness.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / administration & dosage
  • Bevacizumab / therapeutic use*
  • Cetuximab / administration & dosage
  • Cetuximab / therapeutic use*
  • Cohort Studies
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / pathology
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Immunological
  • KRAS protein, human
  • Bevacizumab
  • Proto-Oncogene Proteins p21(ras)
  • Cetuximab