title: A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway.
  
  
  METHODS
  Thirty-eight patients with 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 regimens for metastatic disease. The primary end point was response 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 > or = 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 was well-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.
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. dicklerm@mskcc.org
authors.forename: Maura N
authors.initials: MN
authors.lastname: Dickler
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Carey A
authors.initials: CA
authors.lastname: Eberle
authors.forename: Edi
authors.initials: E
authors.lastname: Brogi
authors.forename: James F
authors.initials: JF
authors.lastname: Caravelli
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yeh
authors.forename: Diana E
authors.initials: DE
authors.lastname: Lake
authors.forename: Chau T
authors.initials: CT
authors.lastname: Dang
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Gilewski
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Bromberg
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Seidman
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: D'Andrea
authors.forename: Mark M
authors.initials: MM
authors.lastname: Moasser
authors.forename: Michele
authors.initials: M
authors.lastname: Melisko
authors.forename: John W
authors.initials: JW
authors.lastname: Park
authors.forename: Janet
authors.initials: J
authors.lastname: Dancey
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride