title: Activity of dalotuzumab, a selective anti-IGF1R antibody, in combination with erlotinib in unselected patients with Non-small-cell lung cancer: a phase I/II randomized trial.
abstract: BACKGROUND
  We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth factor 1 receptor monoclonal antibody (IGF1R MoAb), plus erlotinib in a sequential phase I/II trial in unselected patients with refractory advanced non-small-cell lung cancer (NSCLC).The phase I trial determined the recommended dose and safety of erlotinib plus dalotuzumab at 5 mg/kg or 10 mg/kg weekly in 20 patients. The phase II trial compared outcomes to erlotinib alone and erlotinib plus dalotuzumab at the mg/kg established in the phase I trial.
  
  
  RESULTS
  Erlotinib at 150 mg plus dalotuzumab at 10 mg/kg was safe. The phase II trial included 37 patients in the erlotinib arm and 38 patients in the erlotinib plus dalotuzumab arm. Progression-free survival was 1.6 versus 2.5 months, overall survival was 10.2 and 6.6 months, and the objective response rate was 7.9% and 2.7%, respectively, with no significant differences between the two arms. Grade 3-5 adverse events occurred in 11 (28.9%) versus 13 (35.1%) patients, respectively. The most frequent adverse events were asthenia (36.8% vs. 37.8%), dehydration (5.3% vs. 2.7%), diarrhea (71% vs. 81.1%), hyperglycemia (13.1% vs.18.9%), and skin-related toxicities (92.1% vs. 86.4%).
  
  
  CONCLUSIONS
  The addition of dalotuzumab to erlotinib did not improve efficacy outcome in patients with refractory advanced NSCLC.
authors.affiliation: Catalan Institut of Oncology-Badalona, Hospital Universitari Germans Trias i Pujol and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Moran
authors.affiliation: Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Keedy
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA USA.
authors.forename: Hossein
authors.initials: H
authors.lastname: Borghaei
authors.affiliation: University Health Network Princess Margaret Cancer Centre, University of Toronto, Ontario, Canada.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: Amelia
authors.initials: A
authors.lastname: Insa
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Brown
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Fitzgerald
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Sathyanarayanan
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Reilly
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors.forename: David
authors.initials: D
authors.lastname: Mauro
authors.affiliation: Sanofi Aventis, Bridgewater, NJ USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Hsu
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: UT Southwestern University, Dallas, TX USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
keywords: Dalotuzumab; Epidermal growth factor receptor; Insulin growth factor receptor; Non-small-cell lung cancer; Phase I/II trial