Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II Consortia

Gynecol Oncol. 2008 Jul;110(1):49-55. doi: 10.1016/j.ygyno.2008.02.009. Epub 2008 Apr 18.

Abstract

Objectives: The objectives of this phase II trial were to assess the activity and tolerability of the combination of bevacizumab and erlotinib in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer.

Methods: This was a single arm, multicenter phase II trial with overall objective response as the primary endpoint. Eligible patients had two or fewer prior chemotherapy regimens for recurrent or refractory disease and no prior anti-VEGF or anti-EGFR agents. Bevacizumab, 15 mg/kg, was administered intravenously every 21 days and erlotinib, 150 mg orally, was given daily.

Results: Between July and October 2005, 13 patients were enrolled. There were two major objective responses, one complete response of 16+ month duration and one partial response of 11 month duration, for a response rate of 15% (95% CI 1.9% to 45.4%). Seven patients had a best response of stable disease. The most common grade 3 or 4 toxicities included anemia (n=1), nausea (n=2), vomiting (n=1), hypertension (n=1), and diarrhea (n=2). One patient with an ileostomy was removed from the study secondary to grade 3 diarrhea. Two patients had fatal gastrointestinal perforations.

Conclusion: There was no strong suggestion that this combination was superior to single agent bevacizumab, and the rate of gastrointestinal perforation was of concern. The study was therefore stopped. Identification of risk factors for gastrointestinal perforation will be of importance for the use of bevacizumab in the treatment of ovarian cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Angiogenesis Inhibitors / toxicity
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal / toxicity
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Biomarkers / blood
  • Erlotinib Hydrochloride
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / mortality
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Patient Selection
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / pathology
  • Quinazolines / therapeutic use*
  • Quinazolines / toxicity
  • Safety
  • Survival Rate
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-2 / blood

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Quinazolines
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Erlotinib Hydrochloride
  • Vascular Endothelial Growth Factor Receptor-2