Exploratory modeling and simulation to support development of motesanib in Asian patients with non-small cell lung cancer based on MONET1 study results

Clin Pharmacol Ther. 2014 Apr;95(4):446-51. doi: 10.1038/clpt.2014.11. Epub 2014 Jan 17.

Abstract

The motesanib phase III MONET1 study failed to show improvement in overall survival (OS) in non-small cell lung cancer, but a subpopulation of Asian patients had a favorable outcome. We performed exploratory modeling and simulations based on MONET1 data to support further development of motesanib in Asian patients. A model-based estimate of time to tumor growth was the best of tested tumor size response metrics in a multivariate OS model (P < 0.00001) to capture treatment effect (hazard ratio, HR) in Asian patients. Significant independent prognostic factors for OS were baseline tumor size (P < 0.0001), smoking history (P < 0.0001), and ethnicity (P < 0.00001). The model successfully predicted OS distributions and HR in the full population and in Asian patients. Simulations indicated that a phase III study in 500 Asian patients would exceed 80% power to confirm superior efficacy of motesanib combination therapy (expected HR: 0.74), suggesting that motesanib combination therapy may benefit Asian patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asian People*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Trials, Phase III as Topic
  • Computer Simulation
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Models, Biological*
  • Multivariate Analysis
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Oligonucleotides
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Smoking / epidemiology
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Indoles
  • Oligonucleotides
  • Niacinamide
  • imetelstat