Time to tumor growth (TTG) proved to be the best metric for predicting overall survival in persons with metastatic colorectal cancer receiving bevacizumab with or without chemotherapy.
To assess the efficacy of a new mathematical model of tumor growth inhibition in predicting overall survival in Western and Chinese patients with metastatic colorectal cancer, René Bruno, PhD, of Pharsight Consulting Services Europe (Marseille, France), and colleagues estimated various metrics of tumor size response. Pharsight (St. Louis, Missouri) is part of Certara, a provider of software and scientific consulting services that support translational approaches to drug development. Pharsight developed the mathematical model of tumor growth inhibition.
The tumor size response metrics were estimated using longitudinal tumor size models and data from two phase III studies comparing bevacizumab plus chemotherapy (fluorouracil, leucovorin, and irinotecan) vs chemotherapy alone as first-line treatment in 932 Western and 203 Chinese persons with colorectal cancer.
Bruno’s team evaluated baseline prognostic factors and the tumor size metric estimates in multivariate models to predict overall survival. As the investigators reported in Journal of Clinical Oncology, they used multiple simulations of the phase III studies to test the predictive capabilities of the models.
TTG was found to be the best metric for predicting overall survival. The proposed model worked equally well when predicting overall survival rates for Western and Chinese patients and as such, could be used to support drug development decisions in either population.
“Whereas patients may have long [progression-free survival] as a result of indolent disease, if the tumor is continuously growing, TTG would be quite short. Thus, TTG allows differentiation of drug effect from a favorable prognosis,” wrote Michael L. Maitland, MD, PhD, of the University of Chicago Medicine, Chicago, Illinois, and colleagues in an accompanying editorial.