Combining targeted agents: Blocking the epidermal growth factor and vascular endothelial growth factor pathways

Alan Sandler, Roy Herbst, Paul Bunn, John Heymach, Thomas Lynch, Jeffrey Settleman, Rogerio Lilenbaum, Panos Fidias, Sarada Gurubhagavatula, David Johnson

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Erlotinib HCl is a reversible, highly selective epidermal growth factor receptor tyrosine kinase inhibitor. Additionally, both agents have shown benefit in patients with previously treated non-small cell lung cancer (NSCLC). Preclinical data in xenograft models produced greater growth inhibition with the combination than with either agent alone. A phase I/II study in two centers examined combined erlotinib and bevacizumab treatment in patients with nonsquamous stage IIIB/IV NSCLC with one or more prior chemotherapy. In phase 1,150 mg/d erlotinib orally plus 15 mg/kg bevacizumab i.v. every 21 days was established as the phase II dose. A total of 40 patients were enrolled and treated in this study (34 patients at phase II dose): 21 were female, 30 had adenocarcinoma histology, 9 were never smokers, and 22 had two or more prior regimens. The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between erlotinib and bevacizumab. Eight patients (20.0%) had partial responses and 26 (65.0%) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. Encouraging antitumor activity and safety of erlotinib plus bevacizumab support further development of this combination for patients with advanced NSCLC. A randomized phase II trial has been completed, and a phase III trial is ongoing.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume12
Issue number14
DOIs
StatePublished - Jul 15 2006

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Epidermal Growth Factor
Vascular Endothelial Growth Factor A
Non-Small Cell Lung Carcinoma
Antibodies, Monoclonal, Humanized
Exanthema
Proteinuria
Epidermal Growth Factor Receptor
Heterografts
Protein-Tyrosine Kinases
Disease-Free Survival
Diarrhea
Histology
Adenocarcinoma
Pharmacokinetics
Erlotinib Hydrochloride
Bevacizumab
Safety
Drug Therapy
Survival
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Combining targeted agents : Blocking the epidermal growth factor and vascular endothelial growth factor pathways. / Sandler, Alan; Herbst, Roy; Bunn, Paul; Heymach, John; Lynch, Thomas; Settleman, Jeffrey; Lilenbaum, Rogerio; Fidias, Panos; Gurubhagavatula, Sarada; Johnson, David.

In: Clinical Cancer Research, Vol. 12, No. 14, 15.07.2006.

Research output: Contribution to journalArticle

Sandler, A, Herbst, R, Bunn, P, Heymach, J, Lynch, T, Settleman, J, Lilenbaum, R, Fidias, P, Gurubhagavatula, S & Johnson, D 2006, 'Combining targeted agents: Blocking the epidermal growth factor and vascular endothelial growth factor pathways', Clinical Cancer Research, vol. 12, no. 14. https://doi.org/10.1158/1078-0432.CCR-06-0796
Sandler, Alan ; Herbst, Roy ; Bunn, Paul ; Heymach, John ; Lynch, Thomas ; Settleman, Jeffrey ; Lilenbaum, Rogerio ; Fidias, Panos ; Gurubhagavatula, Sarada ; Johnson, David. / Combining targeted agents : Blocking the epidermal growth factor and vascular endothelial growth factor pathways. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 14.
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