Letter to the editor: Comments on ‘A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation’

Abstract

With great interest, we read the research article of Lala et al. [1]. The authors present a robust population pharmacokinetic (PPK) model of pembrolizumab with data from 2993 patients and a thorough data interpretation. This research gives a better insight into the exposureeeresponse relationship for pembrolizumab, and they concluded that a dose of 2 mg/kg or a fixed dose of 200 mg every 3 weeks (Q3W) can be extended to a dose of 400 mg Q6W based on pharmacokinetic modelling. Although this study provides clear dosing

Alternative dosing strategies for immune checkpoint inhibitors to improve cost-effectiveness: a special focus on nivolumab and pembrolizumab

“…Our current estimates of savings after hybrid dosing are in line with previously estimated savings of 8-13•79% for nivolumab 25,26,37 and 16-26•4% for pembrolizumab 10,25,26,37,41,46 . The published studies show that savings are feasible in Europe 25,37,46 , US 10,26 , Canada 41 , and Asia 40 . Global adoption of the alternative dosing strategies presented in this personal view could lead to over 5 billion euros in savings annually.…”

“…Multiple studies have shown that optimizing dosing schedules can reduce treatment costs 10,25,30,[39][40][41]46 . Our current estimates of savings after hybrid dosing are in line with previously estimated savings of 8-13•79% for nivolumab 25,26,37 and 16-26•4% for pembrolizumab 10,25,26,37,41,46 . The published studies show that savings are feasible in Europe 25,37,46 , US 10,26 , Canada 41 , and Asia 40 .…”

“…Therefore, it has been argued that a six-weekly 4 mg/kg weightbased dose would be equivalent to a three-weekly 2 mg/kg dose and could serve as an alternative dose for six-weekly dosing. 46,47 Simulations by a Canadian agency predicted that sixweekly 4 mg/kg would result in Ctrough,ss of 17•94-38•52 µg/ml in a 70-150 kg body weight individual, which is higher than triweekly 200 mg Ctrough after cycle 1 (table 1). 15,16,42 Hybrid dosing is an especially attractive option for six-weekly dosing since it does not require vial sharing to achieve significant cost reductions.…”

Combatting the rising costs of cancer drugs; interventions from a university hospital’s perspective

“…However, it was demonstrated that weight-based dosing of pembrolizumab was equally effective and safe ( Bayle et al, 2019 ). This published pharmacokinetic model ( Bayle et al, 2019 ) has validated that a dosing regimen of 2 mg/kg Q3W could equate to 4 mg/kg/dose Q6W (with 400 mg as maximum dose) ( Diekstra et al, 2020 ). Within our own clinical setting, as was described in Malmberg et al, the modified dose of 4 mg/kg Q6W with a maximum dose of 400 mg and a dose rounding margin of 10%, has not only provided effective and safe treatment for our patients, but also prevented potential overdose ( Malmberg et al, 2022 ) and reduced costs by 22% (in 2022).…”