title: An Open-Label, Multicenter, Randomized, Phase II Study of Cisplatin and Pemetrexed With or Without Cixutumumab (IMC-A12) as a First-Line Therapy in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer.
abstract: Type 1 insulin-like growth factor receptor is deregulated in solid tumors. Cixutumumab, a monoclonal antibody that inhibits the activity of type 1 insulin-like growth factor receptor, was investigated in combination with pemetrexed/cisplatin in the frontline setting.
  
  
  
  In this open-label, phase II study, patients with stage IV nonsquamous NSCLC and a performance status of 0 to 1 were randomized (1:1) to receive 20 mg/kg cixutumumab, 500 mg/m2pemetrexed, and 75 mg/m2cisplatin (cixutumumab [n = 87]) or pemetrexed and cisplatin (control [n = 85]). Eligible patients received pemetrexed-based maintenance therapy with cixutumumab (cixutumumab arm) or without it (control arm). The primary end point was progression-free survival. Secondary end points assessed overall survival, objective response rate, and safety. Survival was analyzed by the Kaplan-Meier method and Cox proportional hazard model. Exploratory correlative analyses were also performed.
  
  
  
  The mean age of the intent-to-treat population (n = 172) was 59 years (range 32-83). Median progression-free survival was 5.45 months with cixutumumab versus 5.22 months in the control (hazard ratio = 1.15, 95% confidence interval: 0.81-1.61; p = 0.44). Median overall survival was 11.33 months with cixutumumab versus 10.38 months in the control (hazard ratio = 0.93, 95% confidence interval: 0.64-1.36). Objective response rate did not differ between treatments (p = 0.338). Grade 3 or 4 hyperglycemia occurred at a higher rate with cixutumumab than in the control (9.4% versus 1.2%). One death possibly related to cixutumumab occurred.
  
  
  
  Efficacy was not improved in patients with nonsquamous NSCLC when cixutumumab was added to pemetrexed/cisplatin. Combination therapy was well tolerated and no new safety concerns were reported.
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy. Electronic address: silvia.novello@unito.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scagliotti
authors.affiliation: Clinical Oncology Service, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
authors.forename: Gilberto
authors.initials: G
authors.lastname: de Castro
authors.affiliation: Pulmonary Department, Yedikule Chest Disease Hospital, Istanbul, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Kiyik
authors.affiliation: Clinical Research Center of Viedma Clinic, Rio Negro, Argentina.
authors.forename: Rubén
authors.initials: R
authors.lastname: Kowalyszyn
authors.affiliation: Lung Center - Department of Pneumology, Sana Kliniken Düsseldorf, Düsseldorf, Germany.
authors.forename: Karl-Matthias
authors.initials: KM
authors.lastname: Deppermann
authors.affiliation: Medical Oncology, Hospital del Mar, Barcelona, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Arriola
authors.affiliation: Hospital Bois L-Abbaye, Seraing, Belgium.
authors.forename: Lionel
authors.initials: L
authors.lastname: Bosquee
authors.affiliation: Department of Cancer Immunobiology, Eli Lilly and Company, New York, New York.
authors.forename: Ruslan D
authors.initials: RD
authors.lastname: Novosiadly
authors.affiliation: Statistics-Oncology Department, Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Tuan S
authors.initials: TS
authors.lastname: Nguyen
authors.affiliation: Department of Cancer Immunobiology, Eli Lilly and Company, New York, New York.
authors.forename: Amelie
authors.initials: A
authors.lastname: Forest
authors.affiliation: Statistics-Oncology Department, Eli Lilly and Company, Bridgewater, New Jersey.
authors.forename: Shande
authors.initials: S
authors.lastname: Tang
authors.affiliation: Global Pharmacokinetics/Pharmacodynamics and Pharmacometrics, Eli Lilly and Company, Bridgewater, New Jersey.
authors.forename: Siva Rama Prasad
authors.initials: SRP
authors.lastname: Kambhampati
authors.affiliation: Clinical Sciences, Early Phase, Eli Lilly and Company, Bridgewater, New Jersey.
authors.forename: Jan
authors.initials: J
authors.lastname: Cosaert
authors.affiliation: Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068437:Pemetrexed; C557414:cixutumumab; D002945:Cisplatin
keywords: Cixutumumab; First-line therapy; IMC-A12; NSCLC; Pemetrexed