A rational approach to dose optimisation of pembrolizumab and nivolumab using cost analysis and pharmacokinetic modelling and simulation

Background

Pembrolizumab and nivolumab are PDL1 inhibitors approved for the treatment of advanced malignancies. Both are approved based on body size (mg/kg) dosing, which can be associated with significant wastage due to available vial sizes and acquisition cost of the drugs. Dose banding is using a defined set of ranges (±10%) offers an alternative approach to body weight dosing. The aim of this work is to evaluate cost and dosing using pharmacokinetic (PK) simulation and data from 42 patients entered into the MHRA Early Access to Medicines Scheme for pembrolizumab and 24 patients enrolled in checkmate-172 trial for nivolumab.

Methods

Consecutive patients receiving pembrolizumab (n = 42) or nivolumab (n = 24) and with a median weight of 79.5kg (range 44-130kg) and 73.3kg (range 52-103kg) respectively were analysed. The costs were based on 12 weeks of treatment which was the time take to first assessment for both drugs. This was 4 cycles of pembrolizumab every 21 days (Q3W) and 6 cycles of nivolumab every 14 days (Q2W). 1000 random individuals were evaluated in a simulated study for pharmacokinetic and pharmacodynamic assessment. Published population PK models were used to simulate exposure and probability of trough levels achieving target level (10mg/L) required for maximum target engagement or receptor occupancy for pembrolizumab and nivolumab respectively.

Results

The costs of different strategies are illustrated in Table 1. The table also include simulated area under the curve (over the last two cycles) and mean probability of trough levels (after the first cycle of treatment) achieving 10mg/L or receptor occupancy for the different dosing strategies.

*UK cost excluding VAT; company's submission

Conclusions

Banded fixed dose strategies result in comparable levels of exposure and target engagement or receptor occupancy and can offer significant cost reduction. Vial size availability can contribute to the level of savings to be gained.

Clinical trial identification

N/A

Legal entity responsible for the study

Kayode Ogungbenro

Funding

N/A

Disclosure

R. Duncombe: Paid consultant to Bayer; Janssen; Amgen; Pfizer; MSD; Roche; Sanofi Support for travel from Novartis. No funding received for this study. P. Lorigan: Paid consultant to BMS, Merck, Amgen, Novartis, Roche, GSK and Chugai. Support for travel from BMS and Merck. No funding received for this study. All other authors have declared no conflicts of interest.