A phase I study of erlotinib and bevacizumab for recurrent or metastatic squamous cell carcinoma of the head and neck (HNC).

Reviewer: Walter Sall, MD
Last Modified: May 15, 2005

Presenter: E.E.Vokes
Presenter's Affiliation: National Cancer Institute
Type of Session: Scientific


  • Recurrent or metastatic HNC is a challenging clinical problem.  With conventional chemotherapy, Response Rate (RR) is < 30% and Median Survival (MS) is 6-8 months.
  • Gefitinib, a small molecule EGFR receptor tyrosine kinase inhibitor, has been shown to have modest single agent activity in this disease with a RR of 11% and MS of 8.1 months.
  • Erlotinib, a newer EGFR inhibitor, also has modest single agent activity in HNC and has shown a survival benefit in advanced lung cancer.
  • Resistance to EGFR inhibition is common and correlates with increased VEGF expression and poor outcome. 
  • This trial tested the safety and activity of the combination of erlotinib and bevacizumab (BEV), a humanized chimeric monoclonal antibody directed against human VEGF,  previously found to provide a survival benefit in advanced colorectal malignancies.

Materials and Methods

  • Initial phase I trial used fixed dose of erlotinib with increasing BEV dose.
  • Phase II portion tested RR, time to progression (TTP) and MS as well as tissue levels of VEGF in treated patients.
  • Eligibility:  Metastatic or locally recurrent incurable squamous carcinoma in patients having received no more than one prior treatment regimen.  Exclusion criteria included presence of brain metastases, tumor encasing major blood vessels or history of thrombosis or hemorrhage


  • 51 patients entered between 3/2003 and 11/2004.
  • No dose limiting toxicities were observed during phase I.
  • 48 patients treated at the phase II dose of erlotinib 150mg daily and BEV 15mg/kg every 3 weeks. 
  • toxicity: skin rash in 28 of 44 patients, diarrhea in 15 patients, fatigue in 21 patients and grade III or higher hemorrhage in three patients with one hemorrhagic death.
  • 2 complete responses, 5 partial responses, 26 patients with stable disease and 15 with progressive disease were seen.
  • Overall response rate was 14.6% with MS of 6.8 months and 1 year OS of 25%.
  • Tissue and serum VEGF levels were significantly decreased with treatment.
  • MS was 7.5 months and 5.9 months when therapy was given as first line and second line therapy, respectively.

Author's Conclusions

  • BEV and erlotinib can safely be co-administered.  There is no synergistic toxicity.
  • Response Rate is significantly higher than with with either agent alone.  MS is similar to that with chemotherapy alone with less toxicity.


Clinical/Scientific Implications

The combination of BEV and erlotinib gives another potential option for the treatment of this difficult clinical problem.  Further studies in the phase III setting of BEV alone vs erlotinib alone vs the combination may be warranted in order to determine whether the use of both agents together is warranted.  Care certainly needs to be taken in selecting potential patients for this regimen as the risk of hemmorhage may be increased.  For the moment, this combination therapy must still be considered investigational and only offered in clinical trials.