Exploratory Modeling and Simulation to Support Development of Motesanib in Asian Patients With Non–Small Cell Lung Cancer Based on MONET1 Study Results. Issue 4 (17th January 2014)

• Record Type: Journal Article
• Authors: Claret, L; Bruno, R; Lu, J‐F; Sun, Y‐N; Hsu, C‐P
• Is Part Of: Clinical pharmacology & therapeutics. Volume 95:Issue 4(2014)
• Page Start: 446
• Page End: 451
• Publication Date: 2014-01-17
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1038/clpt.2014.11
• Languages: English
• ISSNs: 0009-9236

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 (<italic>P</italic> &lt; 0.00001) to capture treatment effect (hazard ratio, HR) in Asian patients. Significant independent prognostic factors for OS were baseline tumor size (<italic>P</italic> &lt; 0.0001), smoking history (<italic>P</italic> &lt; 0.0001), and ethnicity (<italic>P</italic> &lt; 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.</p> <p> <italic>Clinical Pharmacology &amp; Therapeutics</italic> (2014); <bold>95</bold> 4, 446–451. doi:<ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">10.1038/clpt.2014.11</ext-link></p> </abstract>