Université Paris Cité, Faculté de Pharmacie de Paris, INSERM UMR-S1144, Paris, France.
Biologie du Médicament - Toxicologie, Cochin University Hospital, AP-HP, Paris, France.
Br J Cancer. 2024 May;130(11):1866-1874. doi: 10.1038/s41416-024-02659-x. Epub 2024 Mar 26.
Reducing nivolumab dose intensity could increase patients' life quality and decrease the financial burden while maintaining efficacy. The aims of this study were to develop a population PK model of nivolumab based on data from unselected metastatic cancer patients and to simulate extended-interval regimens allowing to maintain minimal effective plasma concentrations (MEPC).
Concentration-time data (992 plasma nivolumab concentrations, 364 patients) were modeled using a two-compartment model with linear elimination clearance in Monolix software. Extended-interval regimens allowing to maintain steady-state trough concentrations (C) above the MEPC of 2.5 mg/L or 1.5 mg/L in >90% of patients were simulated.
Increasing 3-times the dosing interval from 240 mg every two weeks (Q2W) to Q6W and 2-times from 480 mg Q4W to Q8W resulted in C above 2.5 mg/L in 95.8% and 95.4% of patients, respectively. 240 mg Q8W and 480 mg Q10W resulted in C above 1.5 mg/L in 91.0% and 91.8% of patients, respectively. Selection of a 240 mg Q6W regimen would decrease by 3-fold the annual treatment costs compared to standard regimen of 240 mg Q2W (from 78,744€ to 26,248€ in France).
Clinical trials are warranted to confirm the non-inferiority of extended-interval compared to standard regimen.
降低纳武利尤单抗的剂量强度可以提高患者的生活质量，减轻经济负担，同时保持疗效。本研究旨在建立一个基于未经选择的转移性癌症患者数据的纳武利尤单抗群体药代动力学模型，并模拟延长间隔方案，以维持最小有效血浆浓度（MEPC）。
使用 Monolix 软件中的两室模型和线性消除清除率对浓度-时间数据（992 个纳武利尤单抗血浆浓度，364 名患者）进行建模。模拟了延长间隔方案，使稳态谷浓度（C）维持在 2.5mg/L 或 1.5mg/L 以上，超过 90%的患者。
将每 2 周 240mg 的给药间隔增加 3 倍至 Q6W 和将每 4 周 480mg 的给药间隔增加 2 倍至 Q8W，分别使 95.8%和 95.4%的患者 C 超过 2.5mg/L。240mg Q8W 和 480mg Q10W 分别使 91.0%和 91.8%的患者 C 超过 1.5mg/L。与标准的 240mg Q2W 方案相比，选择 240mg Q6W 方案将使每年的治疗费用降低 3 倍（从法国的 78744 欧元降至 26248 欧元）。
需要进行临床试验以确认延长间隔与标准方案相比的非劣效性。
