title: Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase II study of combination of the anti-insulin-like growth factor 1 receptor antibody CP-751,871 with paclitaxel and carboplatin (PCI) in advanced treatment-naïve non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients were randomly assigned (2:1) to paclitaxel 200 mg/m(2), carboplatin (area under the plasma concentration-time curve of 6), and CP-751,871 10 to 20 mg/kg (PCI(10), PCI(20)) or paclitaxel and carboplatin alone (PC) every 3 weeks for up to six cycles. PCI(10-20) patients could continue CP-751,871 (figitumumab) treatment after chemotherapy discontinuation. Patients treated with PC experiencing disease progression were eligible to receive CP-751,871 at investigator's discretion. An additional nonrandomized single-arm cohort of 30 patients with nonadenocarcinoma tumor histology receiving PCI(20) was enrolled on completion of the randomized study.
  
  
  RESULTS
  A total of 156 patients were enrolled onto the randomized portion of the study. Safety and efficacy information are available for 151 patients (98 patients treated with PCI and 53 patients treated with PC). Forty-eight patients treated with PCI received PCI(10) and 50 patients received PCI(20) in two sequential stages. Twenty of 53 patients treated with PC received CP-751,871 after disease progression. PCI was well tolerated. Fifty-four percent of patients treated with PCI and 42% of patients treated with PC had objective responses. Sixteen of 23 patients assessable for efficacy in the nonrandomized single-arm extension cohort also responded to treatment. Of note, 14 of 18 randomly assigned and 11 of 14 nonrandomly assigned patients treated with PCI with squamous cell carcinoma histology had response to treatment, including nine objective responses in bulky disease. Responses were also observed in two patients with squamous histology receiving CP-751,871 on PC discontinuation. PCI(20)/PC hazard ratio for progression-free survival was 0.8 to 0.56, according to censorship.
  
  
  CONCLUSIONS
  These data suggest that PCI(20) is safe and effective in patients with NSCLC.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Karp
authors.forename: Luis G
authors.initials: LG
authors.lastname: Paz-Ares
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
authors.forename: Linda
authors.initials: L
authors.lastname: Garland
authors.forename: Felipe
authors.initials: F
authors.lastname: Cardenal
authors.forename: L Johnetta
authors.initials: LJ
authors.lastname: Blakely
authors.forename: Peter D
authors.initials: PD
authors.lastname: Eisenberg
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
authors.forename: George
authors.initials: G
authors.lastname: Blumenschein
authors.forename: Faye M
authors.initials: FM
authors.lastname: Johnson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Green
authors.forename: Antonio
authors.initials: A
authors.lastname: Gualberto
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous; D016190:Carboplatin; D017239:Paclitaxel; C525021:figitumumab