title: Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer: SWOG S0536.
abstract: BACKGROUND
  Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC.
  
  
  METHODS
  Patients received with up to six cycles of carboplatin (area under curve 6), paclitaxel (200 mg/m(2)), cetuximab (400 mg/m(2) day 1 then 250 mg/m(2) weekly), and bevacizumab (15 mg/kg) every 21 days. Patients with an objective response or stable disease received maintenance cetuximab (250 mg/m(2) weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression. The primary endpoint was safety as defined by the frequency and severity of hemorrhagic toxicities. Secondary endpoints included response rate, progression-free survival, overall survival, and toxicity. Molecular biomarkers were assessed in an exploratory manner.
  
  
  RESULTS
  The primary endpoint of grade 4 or higher hemorrhage of 2% (95% confidence interval: 0%-7%) met prespecified criteria for safety. One hundred ten patients were enrolled. There were four treatment-related deaths including lung hemorrhage (2), infection (1), and unknown (1). Median progression-free survival was 7 months and median overall survival was 15 months. The response rate was 56% with an overall disease control rate of 77%.
  
  
  CONCLUSIONS
  This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.
authors.affiliation: *Levine Cancer Institute, Charlotte, North Carolina; †SWOG Statistical Center, Seattle, Washington; ‡Yale Cancer Center, New Haven, Connecticut; §Cancer Center of Kansas and Wichita CCOP, Wichita, Kansas; ‖Central Illinois CCOP and Cancer Care Specialists, Decatur, Illinois; ¶University of Colorado Cancer Center, Aurora, Colorado; #University of California Davis Cancer Center, Sacramento, California; and **MD Anderson Cancer Center, Houston, Texas.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kim
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Mary W
authors.initials: MW
authors.lastname: Redman
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Mario R
authors.initials: MR
authors.lastname: Velasco
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel; D000068818:Cetuximab