Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3

Eur J Cancer. 2018 Jan;88:77-86. doi: 10.1016/j.ejca.2017.10.028. Epub 2017 Nov 28.


Background: The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome.

Patients and methods: This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method.

Results: Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001).

Conclusions: Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres. CLINICALTRIALS.

Gov-identifier: NCT00433927.

Keywords: Bevacizumab; Cetuximab; Conversion therapy; Metastatic colorectal cancer; Resection; Surgery.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cetuximab / administration & dosage
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • Combined Modality Therapy
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Irinotecan
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Outcome Assessment, Health Care / methods*
  • Outcome Assessment, Health Care / statistics & numerical data


  • Bevacizumab
  • Irinotecan
  • Cetuximab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Associated data