Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Clin Pharmacol Ther. 2013 Apr;93(4):345-51. doi: 10.1038/clpt.2012.263. Epub 2012 Dec 27.
To improve future drug development efficiency in renal cell carcinoma (RCC), a disease-progression model was developed with longitudinal tumor size data from a phase III trial of sorafenib in RCC. The best-fit model was externally evaluated on 145 placebo-treated patients in a phase III trial of pazopanib; the model incorporated baseline tumor size, a linear disease-progression component, and an exponential drug effect (DE) parameter. With the model-estimated effect of sorafenib on RCC growth, we calculated the power of randomized phase II trials between sorafenib and hypothetical comparators over a range of effects. A hypothetical comparator with 80% greater DE than sorafenib would have 82% power (one-sided α = 0.1) with 50 patients per arm. Model-based quantitation of treatment effect with computed tomography (CT) imaging offers a scaffold on which to develop new, more efficient, phase II trial end points and analytic strategies for RCC.
为提高肾细胞癌（RCC）的未来药物开发效率，对索拉非尼治疗 RCC 的 III 期试验的纵向肿瘤大小数据进行了疾病进展模型的开发。最佳拟合模型在 pazopanib 的 III 期试验的 145 名安慰剂治疗患者中进行了外部评估；该模型纳入了基线肿瘤大小、线性疾病进展成分和指数药物效应（DE）参数。根据模型对索拉非尼对 RCC 生长的影响，我们计算了索拉非尼与假设对照药在一系列效果下的随机 II 期试验的效力。DE 比索拉非尼高 80%的假设对照药，每组 50 例患者，效力为 82%（单侧α=0.1）。基于模型的 CT 成像治疗效果定量为 RCC 提供了新的、更有效的 II 期试验终点和分析策略的框架。
