Time to tumor growth helps predict survival benefit of Bevacizumab for patients with metastatic colorectal cancer

(Press-News.org) ST. LOUIS, MO – May 8, 2013 – Certara™, a leading provider of software and scientific consulting services to improve productivity and decision-making from drug discovery through drug development, announced that its Pharsight Consulting Services has developed a mathematical model of tumor growth inhibition, which when combined with baseline prognostic factors, predicts treatment effect with bevacizumab for patients with metastatic colorectal cancer. These results are now published online in the Journal of Clinical Oncology. A copy of the results can be obtained here, together with a commentary by Michael Maitland, MD, Ph.D., assistant professor of Medicine in the Section of Hematology/Oncology, and associate director, Committee on Clinical Pharmacology and Pharmacogenomics at the University of Chicago Medicine, Chicago, IL.

Researchers estimated several tumor-size response metrics using longitudinal tumor-size models and data from two Phase III clinical trials, which compared bevacizumab with chemotherapy versus chemotherapy alone as first-line therapy for colorectal cancer. Trial participants included 923 Western and 203 Chinese patients. Baseline prognostic factors and the tumor-size metric estimates were assessed in multivariate models to predict overall survival. Multiple simulations of the Phase III studies were used to test the models' predictive capabilities.

Time to tumor growth proved to be the best metric for predicting overall survival. The proposed model worked equally well when predicting overall survival rates for the Western and Chinese patients and as such could be used to support drug development decisions in either population.

René Bruno, Ph.D., managing director of Certara's Pharsight Consulting Services Europe, and senior author of the paper, said: "This approach of combining modeling with longitudinal tumor-size data may contribute to improved design and analysis of more informative early-stage clinical studies (Phase Ib, II). It could also enable researchers to select the most promising treatments and reduce the high attrition rate in Phase III oncology studies."

Robert Powell, PharmD, former senior advisor at Roche China, and co-author of the paper, added: "It is important to know whether patients in a new market (e.g., China, India, Brazil) will be similar to patients in the original US or EU New Drug Application (NDA). While pharmaceutical companies usually assume patients from different regions are the same, there is emerging evidence that they might be different with regard to efficacy, safety and dose response. This type of analysis helps better define Chinese colon cancer response relative to Western patients. Roche performed this combined Chinese and US NDA study analysis to learn whether Chinese patients responded similarly to Western patients so they can use this information to plan future trials. Likewise knowing these results will be important to local regulatory agencies such as the China Food and Drug Administration in this case."

### About Certara Certara is dedicated to improving human health through a broad spectrum of software products and consulting services, from molecular discovery through clinical development, with special focus on supporting translational approaches to drug development. Certara was formed by the acquisition and integration of industry leaders Tripos®, Simcyp™, and Pharsight® Corporation. Each Certara family brand focuses on a key phase within the drug discovery and development process; combined, they offer a unique set of scientific modeling, analysis, and simulation capabilities that can enable the cross-disciplinary approaches necessary for translational science initiatives. For more information, visit http://www.certara.com.

Certara Contact: Diana O'Rourke, 314-951-3310
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