A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial

Ann Oncol. 2013 Sep;24(9):2335-41. doi: 10.1093/annonc/mdt236. Epub 2013 Jun 19.

Abstract

Background: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC).

Patients and methods: Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect.

Results: Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B. The rate of any grade 3/4 toxic effect was 53% in arm A and 13% in arm B. Median PFS was 5.7 months in arm A and 4.2 months in arm B (HR = 0.79; 95% confidence interval 0.55-1.12; P = 0.19). Overall survival (OS) from start of induction chemotherapy was 26.7 months in the randomized population, with no difference between the two arms.

Conclusions: The addition of erlotinib to bevacizumab as maintenance treatment after first-line chemotherapy in mCRC did not improve PFS significantly. On-going clinical and translational studies focus on identifying subgroups of patients that may benefit from erlotinib in the maintenance setting.

Clinical trials number: NCT00598156.

Keywords: bevacizumab; erlotinib; maintenance treatment; metastatic colorectal cancer.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Dänemark
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Maintenance Chemotherapy / methods*
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Schweden
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Protein Kinase Inhibitors
  • Quinazolines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Erlotinib Hydrochloride
  • ErbB Receptors

Associated data

  • ClinicalTrials.gov/NCT00598156