title: Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer.
abstract: OBJECTIVE
  Bevacizumab (Avastin; Genentech, South San Francisco, CA) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody. Erlotinib HCl (Tarceva, OSI-774; OSI Pharmaceuticals, New York, NY) is a potent, reversible, highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical data in various xenograft models produced greater growth inhibition than with either agent alone. Additionally, both agents have demonstrated benefit in patients with previously treated non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  A phase I/II study in two centers examined erlotinib and bevacizumab (A+T) in patients with nonsquamous stage IIIB/IV NSCLC with > or = one prior chemotherapy. In phase I, erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose, although no dose-limiting toxicities were observed. Phase II assessed the efficacy and tolerability of A+T at this dose. Pharmacokinetic parameters were evaluated. ResultsForty patients were enrolled and treated in this study (34 patients at phase II dose); the median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had > or = two prior regimens (three patients had > or = four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between A + T. Eight patients (20.0%; 95% CI, 7.6% to 32.4%) had partial responses and 26 (65.0%; 95% CI, 50.2% to 79.8%) 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.
  
  
  CONCLUSIONS
  Encouraging antitumor activity and safety of A + T support further development of this combination for patients with advanced NSCLC and other solid tumors.
authors.affiliation: Department of Thoracic/Head & Neck Medical Oncology, Biostatistics and Diagnostic Radiology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
authors.forename: Eric
authors.initials: E
authors.lastname: Mininberg
authors.forename: David P
authors.initials: DP
authors.lastname: Carbone
authors.forename: Ted
authors.initials: T
authors.lastname: Henderson
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kim
authors.forename: George
authors.initials: G
authors.lastname: Blumenschein
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.forename: Mylene T
authors.initials: MT
authors.lastname: Truong
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Hai
authors.initials: H
authors.lastname: Tran
authors.forename: Anne
authors.initials: A
authors.lastname: Tsao
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: David A
authors.initials: DA
authors.lastname: Ramies
authors.forename: Robert
authors.initials: R
authors.lastname: Mass
authors.forename: Somasekar
authors.initials: S
authors.lastname: Seshagiri
authors.forename: David A
authors.initials: DA
authors.lastname: Eberhard
authors.forename: Sean K
authors.initials: SK
authors.lastname: Kelley
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride