Jonsson F, Ou Y, Claret L, Siegel D, Jagannath S, Vij R, Badros A, Aggarwal S, Bruno R
Pharsight, a Certara company St. Louis Missouri USA.
Onyx Pharmaceuticals, Inc., an Amgen subsidiary South San Francisco California USA.
CPT Pharmacometrics Syst Pharmacol. 2015 Dec;4(12):711-9. doi: 10.1002/psp4.12044. Epub 2015 Nov 20.
Change in tumor size estimated using longitudinal tumor growth inhibition (TGI) modeling is an early predictive biomarker of clinical outcomes for multiple cancer types. We present the application of TGI modeling for subjects with multiple myeloma (MM). Longitudinal time course changes in M-protein data from relapsed and/or refractory MM subjects who received single-agent carfilzomib in phase II studies (n = 456) were fit to a TGI model. The tumor growth rate estimate was similar to that of other anti-myeloma agents, indicating that the model is robust and treatment-independent. An overall survival model was subsequently developed, which showed that early change in tumor size (ECTS) at week 4, Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, sex, percent bone marrow cell involvement, and number of prior regimens were significant independent predictors for overall survival (P < 0.001). ECTS based on M-protein modeling could be an early biomarker for survival in MM following exposure to single-agent carfilzomib.
使用纵向肿瘤生长抑制（TGI）模型估计的肿瘤大小变化是多种癌症类型临床结局的早期预测生物标志物。我们展示了TGI模型在多发性骨髓瘤（MM）患者中的应用。在II期研究中接受单药卡非佐米治疗的复发和/或难治性MM患者（n = 456）的M蛋白数据的纵向时间进程变化被拟合到一个TGI模型中。肿瘤生长速率估计值与其他抗骨髓瘤药物相似，表明该模型是稳健的且与治疗无关。随后建立了一个总生存模型，该模型显示第4周时的肿瘤大小早期变化（ECTS）、东部肿瘤协作组体能状态（ECOG PS）、血红蛋白、性别、骨髓细胞受累百分比以及既往治疗方案数量是总生存的显著独立预测因素（P < 0.001）。基于M蛋白建模的ECTS可能是MM患者接受单药卡非佐米治疗后生存的早期生物标志物。
