Extending the dosing intervals of nivolumab: model-based simulations in unselected cancer patients

期刊论文
发表日期：

2024年3月26日

查看全文

Alicja Puszkiel,
Guillaume Bianconi,
Blaise Pasquiers,
David Balakirouchenane,
Jennifer Arrondeau,
Pascaline Boudou-Rouquette,
Marie-Claire Bretagne,
Joe-Elie Salem,
Xavier Declèves,
Michel Vidal,
Nora Kramkimel,
Sarah Guegan,
Selim Aractingi,
Olivier Huillard,
Jérôme Alexandre,
Marie Wislez,
François Goldwasser,
Benoit Blanchet

摘要

Background

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).

Methods

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_min,ss) above the MEPC of 2.5 mg/L or 1.5 mg/L in >90% of patients were simulated.

Results

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_min,ss above 2.5 mg/L in 95.8% and 95.4% of patients, respectively. 240 mg Q8W and 480 mg Q10W resulted in C_min,ss 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).

Conclusions

Clinical trials are warranted to confirm the non-inferiority of extended-interval compared to standard regimen.