Evaluation of Continuous Tumor-Size–Based End Points as Surrogates for Overall Survival in Randomized Clinical Trials in Metastatic Colorectal Cancer

Key Points Question Can end points based on the kinetics of tumor size after treatment be used as surrogates for overall survival in metastatic colorectal cancer? Findings In this pooled analysis of data from 20 randomized clinical trials, time to nadir and depth of nadir were modeled and assessed as potential surrogates for overall survival at the patient and trial levels. The associations found were weak or moderate; there were notable differences in tumor-size kinetics between antiangiogenic agents and anti–epidermal growth factor receptor agents. Meaning The implications of these results for early drug development and clinical practice are unclear and warrant further studies; the findings of this study reinforce the need to develop more reliable end points that reflect tumor biology and patient benefit.