Evaluation of tumor-size response metrics to predict overall survival in Western and Chinese patients with first-line metastatic colorectal cancer.

PURPOSE To assess new metrics of tumor-size response to predict overall survival (OS) in colorectal cancer (CRC) in Western and Chinese patients. PATIENTS AND METHODS Various metrics of tumor-size response were estimated using longitudinal tumor size models and data from two phase III studies that compared bevacizumab plus chemotherapy versus chemotherapy as first-line therapy in Western (n = 923) and Chinese (n = 203) patients with CRC. Baseline prognostic factors and tumor-size metrics estimates were assessed in multivariate models to predict OS. Predictive performances of the models were assessed by simulating multiple replicas of the phase III studies. RESULTS Time to tumor growth (TTG) was the best metric to predict OS. TTG fully captured bevacizumab effect. Chinese ethnicity had no impact on OS or on the TTG-OS relationships. The model correctly predicted OS distributions in each arm as well as bevacizumab hazard ratio (model prediction, 0.75 v 0.68 observed in Western patients; 95% prediction interval, 0.62 to 0.91). CONCLUSION TTG captured therapeutic benefit with bevacizumab in first-line CRC patients. Chinese ethnicity had no impact. Longitudinal tumor size data coupled with model-based approaches may offer a powerful alternative in the design and analysis of early clinical studies.