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

Chao H. Huang, Stephen K. Williamson, Prakash Neupane, Sarah A. Taylor, Ace Allen, Nora J. Smart, Adelina M. Uypeckcuat, Sarah Spencer, Jo Wick, Holly Smith, Peter J. Van Veldhuizen, Karen Kelly

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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/m2 and C at 75 mg/m2 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. 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.

Original languageEnglish (US)
Article number301
JournalFrontiers in Oncology
Volume5
Issue numberJAN
DOIs
StatePublished - 2016

Keywords

  • Dalotuzumab
  • IGF-1R
  • Metastatic
  • Non-squamous cell lung cancer
  • Pemetrexed
  • Treatment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Huang, C. H., Williamson, S. K., Neupane, P., Taylor, S. A., Allen, A., Smart, N. J., Uypeckcuat, A. M., Spencer, S., Wick, J., Smith, H., Van Veldhuizen, P. J., & Kelly, K. (2016). Impact study: MK-0646 (Dalotuzumab), insulin growth factor 1 receptor antibody combined with pemetrexed and cisplatin in stage IV metastatic non-squamous lung cancer. Frontiers in Oncology, 5(JAN), [301]. https://doi.org/10.3389/fonc.2015.00301