N. de Rouw (1,2), M. de Boer (3), R.J. Boosman (4), M.M. van den Heuvel (5), D.M. Burger (1), J.E. Lieverse (6), H.J. Derijks (1,2), G.W. Frederix (7), R. ter Heine (2)
(1) Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands, (2) Department of Pharmacy, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands, (3) Utrecht University, School of Pharmacy, Utrecht, The Netherlands, (4) Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek – The Netherlands Cancer Institute, Amsterdam, The Netherlands, (5) Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Pulmonology, Nijmegen, The Netherlands, (6) Department of Pharmacy, HAGA Hospital, The Hague, The Netherlands, (7) Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands
Objectives: Pemetrexed is an antifolate used in the treatment of lung cancer, in combination with other agents or as monotherapy. Currently, pemetrexed dosing is based on body surface area (BSA) [1]. Total systemic clearance of pemetrexed is primarily determined by renal function. Dosing on BSA does not take renal function into account, and shows variability in exposure and pharmacodynamic response [2,3]. This results in unnecessary pemetrexed-related neutropenia and associated costs of treatment. Dose individualization based on renal function might prevent this as it will likely result in less pemetrexed-related neutropenia, thereby reducing treatment costs. However, the costs of treatment of pemetrexed-induced neutropenia are unknown. Therefore, the aims of this study were 1) investigate the costs of pemetrexed-related neutropenia and 2) to determine the budget impact and yearly cost savings of standard dosing versus individualized dosing for pemetrexed.
Methods: Retrospective data on the treatment of ≥ grade 3 neutropenia (defined as absolute neutrophil count <1.0*109/L) during pemetrexed-based chemotherapy was collected from three Dutch hospitals to determine the mean health care consumption of the treatment components: emergency visit, hospitalization (hospitalization days and medication used) and extra white blood cell counts (WBC). For each component, the costs were determined and multiplied by the mean consumption (units) to obtain the mean costs per component. Monte Carlo simulations were performed using a previously validated pharmacokinetic/pharmacodynamic (PK/PD) model to examine the expected neutropenia incidence during four cycles for the following pemetrexed dosing strategies: BSA-based dosing, area under the curve (AUC-) based dosing and time-above-threshold (TAT-) based dosing. The treatments costs per neutropenia and the expected neutropenia incidence were combined to calculate the budget impact and cost savings.
Results: The retrospective dataset contained data of 254 neutropenic episodes. Emergency visits were required in 26.4% of the events and hospitalization in 28.0%. Mean treatment of neutropenia consisted of 2.48 hospitalization days and 1.38 extra WBC. This resulted in mean treatment costs of € 1,490 for a pemetrexed-related neutropenic episode. The mean (±SD) dose administered in the BSA-, TAT- and AUC-based dosing group was 904 (118), 803 (181) and 1194 (869) mg, respectively. The neutropenia incidence was 12.7, 9.9 and 9.7% for BSA-, AUC- and TAT-based dosing of pemetrexed, respectively. Based on a patient population of 4,000, total neutropenia treatment costs were calculated to be approximately € 3.0 million, €2.4 million and €2.3 million, resp. This implicates that total cost savings could be € 686,001 for AUC-based dosing and € 734,317 for TAT-based dosing compared to BSA-based dosing.
Conclusions: Dosing of pemetrexed based on AUC or TAT instead of BSA resulted in a reduced incidence of neutropenia, thereby reducing the treatment costs of pemetrexed. This will probably result in less hospitalization and mortality in the treated population. Improved pemetrexed dose individualization is favorable for both the patient and the payer.
References:
[1] European Medicine Agency. ALIMTA EPAR – Summary of Product Characteristics. 2017
[2] de Rouw N, Boosman RJ, Huitema ADR, Hilbrands LB, Svensson EM, Derijks HJ, et al. Rethinking the Application of Pemetrexed for Patients with Renal Impairment: A Pharmacokinetic Analysis. Clin Pharmacokinet 2021 Jan 09.
[3] Latz JE, Rusthoven JJ, Karlsson MO, Ghosh A, Johnson RD. Clinical application of a semimechanistic-physiologic population PK/PD model for neutropenia following pemetrexed therapy. Cancer Chemother Pharmacol 2006 Apr;57(4):427-435.
Reference: PAGE 29 (2021) Abstr 9601 [www.page-meeting.org/?abstract=9601]
Poster: Drug/Disease Modelling - Oncology