Wang X, Feng Y, Bajaj G, Gupta M, Agrawal S, Yang A, Park J-S, Lestini B, Roy A
Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
Oncology Global Clinical Research, Bristol-Myers Squibb, Princeton, New Jersey, USA.
CPT Pharmacometrics Syst Pharmacol. 2017 Jan;6(1):40-48. doi: 10.1002/psp4.12133. Epub 2016 Dec 26.
To inform the benefit-risk assessment of nivolumab in patients with advanced melanoma, analyses of efficacy and safety exposure-response (E-R) relationships were conducted with data from patients with advanced melanoma enrolled in two clinical studies (phase I and phase III) who received nivolumab 0.1-10.0 mg/kg every 2 weeks. E-R efficacy analyses were performed by relating the nivolumab time-averaged concentration after the first dose (C ) to two endpoints: RECIST objective response (OR) and overall survival (OS). E-R safety analyses characterized the relationship between nivolumab C and the hazard of all-causality adverse events leading to discontinuation or death (AE-DC/D). Nivolumab exposure represented by C was not a significant predictor of OR, OS, or the hazard of AE-DC/D. E-R efficacy and safety relationships were relatively flat over the exposure range.
为了评估纳武利尤单抗在晚期黑色素瘤患者中的获益-风险，利用两项临床研究（I期和III期）中晚期黑色素瘤患者的数据进行了疗效和安全性暴露-反应（E-R）关系分析，这些患者每2周接受0.1-10.0mg/kg纳武利尤单抗治疗。通过将首剂后纳武利尤单抗的时间平均浓度（C）与两个终点关联来进行E-R疗效分析：RECIST客观缓解（OR）和总生存期（OS）。E-R安全性分析描述了纳武利尤单抗C与导致停药或死亡的全因性不良事件（AE-DC/D）风险之间的关系。以C表示的纳武利尤单抗暴露不是OR、OS或AE-DC/D风险的显著预测因素。在暴露范围内，E-R疗效和安全性关系相对平缓。
