First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study

Oncologist. 2012;17(1):15-25. doi: 10.1634/theoncologist.2011-0249. Epub 2012 Jan 10.

Abstract

Purpose: The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC).

Patients and methods: Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety.

Results: The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0-53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand-foot syndrome, and neuropathy.

Conclusion: Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Capecitabine
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Induction Chemotherapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Oxaloacetates
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Oxaloacetates
  • Oxaliplatin
  • Deoxycytidine
  • Bevacizumab
  • Capecitabine
  • Fluorouracil

Supplementary concepts

  • XELOX