NON-SMALL CELL LUNG CANCER (NSCLC) DISEASE-TRIAL MODEL
Purpose and Scope
The developed NSCLC disease model represents an exploratory tool for the purpose of improving oncology drug development. Specifically, the NSCLC disease-trial model is intended to aid in go/no-go decisions early based on effects on tumor size and design of late phase clinical trials including dose-selection.
Data
Four registration trials for NSCLC provided nine different regimens that are either first-line or second-line treatments for locally advanced or metastatic NSCLC.
NSCLC Disease Model
Baseline Risk Factors
Among 11 potential baseline risk factors for survival, ECOG score and baseline tumor size were found to be significantly related to survival in almost all regimens based on a Cox-proportional hazard model.
Tumor Model
Longitudinal tumor size data were described with a dynamic model that incorporates both the tumor growth property and the treatment regimen’s anti-tumor activity.
Survival Model
A parametric survival model was developed to link the identified baseline risk factors (ECOG score and baseline tumor size) and change in tumor size as predictors for patient survival time.
References
Wang Y, Sung C, Dartois C, Ramchandani R, Booth BP, Rock E, and Gobburu J. Elucidation of Relationship Between Tumor Size and Survival in Non-Small-Cell Lung Cancer Patients Can Aid Early Decision Making in Clinical Drug Development. Clin Pharmacol Ther. 2009, Aug 86(2):164-174. (http://www.nature.com/clpt/journal/v86/n2/abs/clpt200964a.html)
FDA Advisory Committee for Pharmaceutical Science and Clinical Pharmacology Meeting, March 18-19, 2008 (http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4351b1-00-index.htm)
On the Use and Value of Drug-Independent Survival Models to Support Clinical Drug Development in Oncology
(http://www.pharsight.com/library/FDA%20Advisory%20Committtee%20Presentation%203-18-08.pdf)
Model-Based Prediction of Phase III Overall Survival in Colorectal Cancer on the Basis of Phase II Tumor Dynamics (http://jco.ascopubs.org/cgi/content/full/27/25/4103)
Claret L, Girard P, Hoff PM, Van Cutsem E, Zuideveld KP, Jorga K, Fagerberg J, Bruno R. Model-Based Prediction of Phase III Overall Survival in Colorectal Cancer on the Basis of Phase II Tumor Dynamics. Journal of Clinical Oncology, Vol 27, No 25 (September 1), 2009: pp. 4103-4108. (http://jco.ascopubs.org/cgi/content/full/27/25/4103)
