Evaluation of Tumor-Size Response Metrics to Predict Overall Survival in Western and Chinese Patients With First-Line Metastatic Colorectal Cancer
A partir de données de deux essais de phase III évaluant l'intérêt d'ajouter le bévacizumab à une chimiothérapie de première ligne et incluant au total 1 126 patients occidentaux ou asiatiques atteints d'un cancer colorectal, cette étude évalue l'association entre des paramètres liés à la croissance tumorale et la survie globale des patients
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.
Journal of Clinical Oncology , résumé, 2013