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

被引:17
作者
Claret, L. [1 ]
Bruno, R. [1 ]
Lu, J-F [2 ]
Sun, Y-N [2 ]
Hsu, C-P [2 ]
机构
[1] Pharsight, Marseille, France
[2] Amgen Inc, Thousand Oaks, CA 91320 USA
关键词
TUMOR-SIZE; MULTIKINASE INHIBITOR; PHASE-III; SURVIVAL; PREDICT; EVALUATE; AMG-706; DESIGN;
D O I
10.1038/clpt.2014.11
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:446 / 451
页数:6
相关论文
共 16 条
[1]  
Bender B.C., 2013, BR J CLIN PHARM
[2]   On the Use of Change in Tumor Size to Predict Survival in Clinical Oncology Studies: Toward a New Paradigm to Design and Evaluate Phase II Studies [J].
Bruno, R. ;
Claret, L. .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2009, 86 (02) :136-138
[3]  
Bruno R, 2011, BLOOD, V118, P1881
[4]  
Claret L, 2006, J CLIN ONCOL, V24, p307S
[5]   Simulations Using a Drug-Disease Modeling Framework and Phase II Data Predict Phase III Survival Outcome in First-Line Non-Small-Cell Lung Cancer [J].
Claret, L. ;
Lu, J-F ;
Bruno, R. ;
Hsu, C-P ;
Hei, Y-J ;
Sun, Y-N .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2012, 92 (05) :631-634
[6]   Evaluation of Tumor-Size Response Metrics to Predict Overall Survival in Western and Chinese Patients With First-Line Metastatic Colorectal Cancer [J].
Claret, Laurent ;
Gupta, Manish ;
Han, Kelong ;
Joshi, Amita ;
Sarapa, Nenad ;
He, Jing ;
Powell, Bob ;
Bruno, Rene .
JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (17) :2110-2114
[7]   Model-Based Prediction of Phase III Overall Survival in Colorectal Cancer on the Basis of Phase II Tumor Dynamics [J].
Claret, Laurent ;
Girard, Pascal ;
Hoff, Paulo M. ;
Van Cutsem, Eric ;
Zuideveld, Klaas P. ;
Jorga, Karin ;
Fagerberg, Jan ;
Bruno, Rene .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (25) :4103-4108
[8]  
Ichinose Y, 2012, J CLIN ONCOL, V30
[9]   Design of phase II cancer trials using a continuous endpoint of change in tumor size: Application to a study of sorafenib and erlotinib in non-small-cell lung cancer [J].
Karrison, Theodore G. ;
Maitland, Michael L. ;
Stadler, Walter M. ;
Ratain, Mark J. .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2007, 99 (19) :1455-1461
[10]  
LAVIN PT, 1981, CANCER CLIN TRIALS, V4, P451