title: Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer.
abstract: OBJECTIVE
  Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, and erlotinib, a reversible, orally available epidermal growth factor receptor tyrosine kinase inhibitor, have demonstrated evidence of a survival benefit in the treatment of non-small-cell lung cancer (NSCLC). A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy, with a favorable safety profile.
  
  
  METHODS
  A multicenter, randomized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy (docetaxel or pemetrexed) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone, as measured by progression-free survival (PFS). All patients had histologically confirmed nonsquamous NSCLC that had progressed during or after one platinum-based regimen.
  
  
  RESULTS
  One hundred twenty patients were randomly assigned and treated. No unexpected adverse events were noted. Fewer patients (13%) in the bevacizumab-erlotinib arm discontinued treatment as a result of adverse events than in the chemotherapy alone (24%) or bevacizumab-chemotherapy (28%) arms. The incidence of grade 5 hemorrhage in patients receiving bevacizumab was 5.1%. Although not statistically significant, relative to chemotherapy alone, the risk of disease progression or death was 0.66 (95% CI, 0.38 to 1.16) among patients treated with bevacizumab-chemotherapy and 0.72 (95% CI, 0.42 to 1.23) among patients treated with bevacizumab-erlotinib. One-year survival rate was 57.4% for bevacizumab-erlotinib and 53.8% for bevacizumab-chemotherapy compared with 33.1% for chemotherapy alone.
  
  
  CONCLUSIONS
  Results for PFS and overall survival favor combination of bevacizumab with either chemotherapy or erlotinib over chemotherapy alone in the second-line setting. No unexpected safety signals were noted. The rate of fatal pulmonary hemorrhage was consistent with previous bevacizumab trials. The toxicity profile of the bevacizumab-erlotinib combination is favorable compared with either chemotherapy-containing group.
authors.affiliation: The M.D. Anderson Cancer Center, Houston, TX 77030, USA. rherbst@mdanderson.org
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: O'Neill
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Philip D
authors.initials: PD
authors.lastname: Bonomi
authors.forename: Lowell
authors.initials: L
authors.lastname: Hart
authors.forename: Ostap
authors.initials: O
authors.lastname: Melnyk
authors.forename: David
authors.initials: D
authors.lastname: Ramies
authors.forename: Ming
authors.initials: M
authors.lastname: Lin
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D011799:Quinazolines; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D000068258:Bevacizumab; D006147:Guanine; D000069347:Erlotinib Hydrochloride