Exploratory Modeling and Simulation to Support Development of Motesanib in Asian Patients With Non–Small Cell Lung Cancer Based on MONET1 Study Results

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