A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer Journal Article


Authors: Dickler, M. N.; Rugo, H. S.; Eberle, C.; Brogi, E.; Caravelli, J.; Panageas, K. S.; Boyd, J.; Yeh, B.; Lake, D. E.; Dang, C.; Gilewski, T. A.; Bromberg, J. F.; Seidman, A. D.; D'Andrea, G.; Moasser, M. M.; Melisko, M.; Park, J. W.; Dancey, J.; Norton, L.; Hudis, C. A.
Article Title: A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer
Abstract: Purpose: To evaluate the efficacy and toxicity of erlotinib plusbevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway. Experimental Design: Thirty-eight patientswith MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimensfor metastatic disease. The primary end point wasresponse rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of ≥26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis. Results: One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy. Conclusions: The combination of erlotinib and bevacizumab waswell-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy. © 2008 American Association for Cancer Research.
Keywords: immunohistochemistry; vasculotropin; adult; clinical article; controlled study; protein expression; treatment outcome; treatment response; aged; middle aged; clinical trial; drug tolerability; fatigue; bevacizumab; doxorubicin; erlotinib; cancer combination chemotherapy; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug withdrawal; hypertension; paclitaxel; adjuvant therapy; antineoplastic agent; biological marker; metastasis; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; breast cancer; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; dehydration; myalgia; epidermal growth factor receptor; cyclophosphamide; pathology; mutational analysis; breast neoplasms; docetaxel; monoclonal antibody; arthralgia; lymphocytopenia; pruritus; rash; antibodies, monoclonal; multicenter study; thrombosis; breast tumor; acne; gefitinib; loperamide; taxane derivative; toxicity; trastuzumab; anthracycline; dyspepsia; dry eye; dry skin; quinazolines; tetracycline; epistaxis; vasculotropin antibody; proteinuria; quinazoline derivative; epidermal growth factor receptor antibody; skin allergy; low back pain
Journal Title: Clinical Cancer Research
Volume: 14
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2008-12-01
Start Page: 7878
End Page: 7883
Language: English
DOI: 10.1158/1078-0432.ccr-08-0141
PUBMED: 19047117
PROVIDER: scopus
PMCID: PMC2748748
DOI/URL:
Notes: --- - "Cited By (since 1996): 24" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Mark M Moasser
    55 Moasser
  2. Andrew D Seidman
    244 Seidman
  3. Clifford Hudis
    840 Hudis
  4. Larry Norton
    563 Norton
  5. Jacqueline Bromberg
    104 Bromberg
  6. Chau Dang
    156 Dang
  7. Diana E Lake
    70 Lake
  8. Maura N Dickler
    237 Dickler
  9. Jeffrey Boyd
    111 Boyd
  10. Katherine S Panageas
    327 Panageas
  11. Edi Brogi
    304 Brogi
  12. Carey Eberle
    17 Eberle