Skip to main content
eScholarship
Open Access Publications from the University of California

Impact study: MK-0646 (Dalotuzumab), insulin growth factor 1 receptor antibody combined with pemetrexed and cisplatin in stage IV metastatic non-squamous lung cancer

  • Author(s): Huang, CH
  • Williamson, SK
  • Neupane, P
  • Taylor, SA
  • Allen, A
  • Smart, NJ
  • Uypeckcuat, AM
  • Spencer, S
  • Wick, J
  • Smith, H
  • Van Veldhuizen, PJ
  • Kelly, K
  • et al.
Abstract

© 2016 Huang, Williamson, Neupane, Taylor, Allen, Smart, Uypeckcuat, Spencer, Wick, Smith, Van Veldhuizen and Kelly. 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/m2and C at 75 mg/m2IV 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. Conclusion: 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.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View