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Exploratory Modeling and Simulation to Support Development of Motesanib in Asian Patients With Non–Small Cell Lung Cancer Based on MONET1 Study Results
Author(s) -
Claret L,
Bruno R,
Lu JF,
Sun YN,
Hsu CP
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2014.11
Subject(s) - medicine , lung cancer , multivariate analysis , hazard ratio , oncology , population , multivariate statistics , exploratory research , exploratory analysis , confidence interval , statistics , computer science , mathematics , environmental health , data science , sociology , anthropology
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. Clinical Pharmacology & Therapeutics (2014); 95 4, 446–451. doi: 10.1038/clpt.2014.11