title: Impact Study: MK-0646 (Dalotuzumab), Insulin Growth Factor 1 Receptor Antibody Combined with Pemetrexed and Cisplatin in Stage IV Metastatic Non-squamous Lung Cancer.
abstract: BACKGROUND
  Insulin-like growth factor 1 receptor (IGF-1R) regulates cell growth, proliferation, and apoptosis. Adenocarcinoma and never-smokers have a higher expression of IGF-1R, which is associated with worse overall survival. Dalotuzumab-MK0646 (D) is a humanized monoclonal antibody that targets IGF-1R. Pemetrexed (P) has higher activity in non-squamous lung cancer (NSQL). We initiated a randomized phase II trial to test the combination of P and Cisplatin (C) ± D in NSQL.
  
  
  METHODS
  Eligibility criteria were untreated NSQL stage IV, ECOG 0 or 1, measurable disease, adequate renal, hepatic and hematologic function, and no other intercurrent illness. P at 500 mg/m(2) and C at 75 mg/m(2) IV were given every 3 weeks. D was given at 10 mg/kg IV weekly on days 1, 8, and 15 of every 3-week cycle in the experimental group. The patients had a radiographic assessment after every two cycles and were treated for a maximum of six cycles if there was a response or stable disease. The primary objective of the study was to compare the clinical response rates of PC vs. PC + D.
  
  
  RESULTS
  From 1/2009 to 2/2011, the study accrued 26 subjects: 16 male and 10 female, with a median age of 59; 14 were treated with PC and 12 were treated with PC + D. We observed two partial responses (PR), seven stable disease (SD), three progressive disease (PD), and two not evaluable (NE) in the PC arm. In comparison, for the PC + D arm, there were three PR, four SD, four PD, and one NE. The hematologic toxicity was similar in both groups. There was higher incidence of hyperglycemia in the experimental group; four cases with grade 3 and one case with grade 4.
  
  
  CONCLUSIONS
  PC + D had a similar response rate compared to PC, with a higher rate of hyperglycemia. Identification of responders using predictive markers would be key to continuing the study of D in NSQL.
  
  
  BACKGROUND
  NCT00799240, clinicaltrials.gov.
authors.affiliation: Kansas City Veterans Administration Medical Center, Kansas City, MO, USA; University of Kansas Cancer Center, Westwood, KS, USA.
authors.forename: Chao H
authors.initials: CH
authors.lastname: Huang
authors.affiliation: University of Kansas Cancer Center , Westwood, KS , USA.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Williamson
authors.affiliation: University of Kansas Cancer Center , Westwood, KS , USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Neupane
authors.affiliation: University of Kansas Cancer Center , Westwood, KS , USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Taylor
authors.affiliation: Kansas City Veterans Administration Medical Center , Kansas City, MO , USA.
authors.forename: Ace
authors.initials: A
authors.lastname: Allen
authors.affiliation: University of Kansas Cancer Center , Westwood, KS , USA.
authors.forename: Nora J
authors.initials: NJ
authors.lastname: Smart
authors.affiliation: Kansas City Veterans Administration Medical Center , Kansas City, MO , USA.
authors.forename: Adelina M
authors.initials: AM
authors.lastname: Uypeckcuat
authors.affiliation: Kansas City Veterans Administration Medical Center , Kansas City, MO , USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Spencer
authors.affiliation: Department of Biostatistics, University of Kansas , Kansas City, KS , USA.
authors.forename: Jo
authors.initials: J
authors.lastname: Wick
authors.affiliation: University of Kansas Cancer Center , Westwood, KS , USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Smith
authors.affiliation: Kansas City Veterans Administration Medical Center, Kansas City, MO, USA; University of Kansas Cancer Center, Westwood, KS, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Van Veldhuizen
authors.affiliation: University of California Davis Comprehensive Cancer Center , Sacramento, CA , USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
keywords: IGF-1R; dalotuzumab; metastatic; non-squamous cell lung cancer; pemetrexed; treatment