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.
Pharsight-A Certara Company, Marseille, France.
L
L
Claret
Pharsight-A Certara Company, Marseille, France.
R
R
Bruno
Amgen, Thousand Oaks, California, USA.
J-F
JF
Lu
Amgen, Thousand Oaks, California, USA.
Y-N
YN
Sun
Amgen, Thousand Oaks, California, USA.
C-P
CP
Hsu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008954:Models, Biological; D015999:Multivariate Analysis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009841:Oligonucleotides; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012907:Smoking / Q000453:epidemiology; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; C519562:imetelstat