Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases

J Clin Oncol. 2013 Jun 1;31(16):1931-8. doi: 10.1200/JCO.2012.44.8308. Epub 2013 Apr 8.

Abstract

Purpose: To assess the effects of cetuximab plus chemotherapy as first-line treatment for unresectable colorectal liver metastases (CLMs).

Patients and methods: After resection of their primary tumors, patients with KRAS wild-type synchronous nonresectable liver-limited metastases from colorectal cancer were randomly assigned to receive chemotherapy (FOLFIRI [fluorouracil, leucovorin, and irinotecan] or mFOLFOX6 [modified fluorouracil, leucovorin, and oxaliplatin]) plus cetuximab (arm A) or chemotherapy alone (arm B). The primary end point was the rate of patients converted to resection for liver metastases. Secondary end points included tumor response and survival.

Results: The intent-to-treat population comprised 138 patients; 70 patients were randomly assigned to arm A and 68 to arm B. After a median of 25.0 months of follow-up, the 3-year overall survival (OS) rate and median survival time (MST) for all patients were 30% and 24.4 months, respectively. The R0 resection rates for liver metastases were 25.7% (18 of 70 patients) in arm A and 7.4% (five of 68 patients) in arm B, which were significantly different (P < .01). Patients in arm A had improved objective response rates (57.1% v 29.4%; P < .01), increased 3-year OS rate (41% v 18%; P = .013) and prolonged MST (30.9 v 21.0 months; P = .013) compared with those in arm B. In addition, in arm A, patients who had resection of liver metastases had a significantly improved MST (46.4 v 25.7 months; P < .01) compared with those who did not undergo surgery.

Conclusion: For patients with initially unresectable KRAS wild-type CLMs, cetuximab combined with chemotherapy improved the resectability of liver metastases and improved response rates and survival compared with chemotherapy alone.

Trial registration: ClinicalTrials.gov NCT01564810.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian People / genetics
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cetuximab
  • China
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Female
  • Fluorouracil / administration & dosage
  • Hepatectomy*
  • Humans
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Research Design
  • Treatment Outcome
  • ras Proteins / genetics*

Substances

  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol

Associated data

  • ClinicalTrials.gov/NCT01564810