Title: Model-based prediction of phase III overall survival in colorectal cancer on the basis of phase II tumor dynamics
Authors: Claret, Laurent ×
Girard, Pascal
Hoff, Paulo M
Van Cutsem, Eric
Zuideveld, Klaas P
Jorga, Karin
Fagerberg, Jan
Bruno, René #
Issue Date: Sep-2009
Publisher: Grune & Stratton
Series Title: Journal of Clinical Oncology vol:27 issue:25 pages:4103-4108
Abstract: PURPOSE: We developed a drug-disease simulation model to predict antitumor response and overall survival in phase III studies from longitudinal tumor size data in phase II trials. METHODS: We developed a longitudinal exposure-response tumor-growth inhibition (TGI) model of drug effect (and resistance) using phase II data of capecitabine (n = 34) and historical phase III data of fluorouracil (FU; n = 252) in colorectal cancer (CRC); and we developed a parametric survival model that related change in tumor size and patient characteristics to survival time using historical phase III data (n = 245). The models were validated in simulation of antitumor response and survival in an independent phase III study (n = 1,000 replicates) of capecitabine versus FU in CRC. RESULTS: The TGI model provided a good fit of longitudinal tumor size data. A lognormal distribution best described the survival time, and baseline tumor size and change in tumor size from baseline at week 7 were predictors (P < .00001). Predicted change of tumor size and survival time distributions in the phase III study for both capecitabine and FU were consistent with observed values, for example, 431 days (90% prediction interval, 362 to 514 days) versus 401 days observed for survival in the capecitabine arm. A modest survival improvement of 39 days (90% prediction interval, -21 to 110 days) versus 35 days observed was predicted for capecitabine. CONCLUSION: The modeling framework successfully predicted survival in a phase III trial on the basis of capecitabine phase II data in CRC. It is a useful tool to support end-of-phase II decisions and design of phase III studies.
ISSN: 0732-183X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
Clinical Digestive Oncology (+)
× corresponding author
# (joint) last author

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