The Pharmacoeconomic Benefits of Pemetrexed Dose Individualization in Patients With Lung Cancer

Abstract

Neutropenia is a dose-related treatment-limiting and costly adverse event of pemetrexed. We postulate that individualized dosing reduces the incidence of neutropenia. The aims of this study were (i) to investigate the costs of pemetrexed-related neutropenia and (ii) to determine the pharmacoeconomic benefits of individualized dosing of pemetrexed in terms of budget impact, yearly cost savings, and reduction in severe neutropenia. Retrospective data on the treatment of grade 3 or higher neutropenia during pemetrexed-based chemotherapy were collected from three Dutch hospitals to determine the mean healthcare consumption during a neutropenic episode. Subsequently, Monte Carlo simulations were performed using a validated pharmacokinetic/pharmacodynamic model to predict the neutropenia incidence during four cycles for standard dosing of pemetrexed and individualized dosing. The mean costs per neutropenia and the expected neutropenia incidence were combined to calculate the budget impact and cost savings. We found that the average costs per pemetrexed-associated neutropenic episode to be €1,490 (US $1,674). The neutropenia incidence for the standard and individualized pemetrexed dosing strategies were 12.7% and 9.9%, respectively. This resulted in total expected neutropenia-related costs of ~ €3.0 million (US $3.372 million) and €2.4 million (US $2.697 million), respectively. Taking the number of patients eligible for pemetrexed treatment into account, individualized dosing could result in saving €686,000 (US $770,995) on a yearly basis in the Netherlands alone. Individualized dosing of pemetrexed can decrease the incidence of neutropenia and thus result in a significant decrease in neutropenia-related costs and decreased risk of hospitalization or even death while maintaining therapeutic exposure.

Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial

“…The AUC range obtained in the subjects with pemetrexed dose based on CKD-EPI is similar to that reported in this study (AUC (median [IQR]) 158 [136-183] mg × h/L versus 154. 7 [137.6-171.5] mg × h/L) [18]. Cachexia is often observed in patients with lung cancer [19,20], resulting in seemingly low serum creatinine concentrations and thus overestimation of renal function.…”

SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells

“…Despite improvements in surgery, radiotherapy, chemotherapy, and targeted therapy, the prognosis for lung cancer patients remains suboptimal, with a five-year survival rate of about 10%-20% [ 4 ]. Pemetrexed (PEM) is an anti-tumor drug that blocks the release process of enzymes required for purine and pyrimidine synthesis, thereby sustaining cell division activities in the S phase and significantly inhibiting the growth of cancer cells [ 5 ]. PEM has been approved as a first-line chemotherapy agent for non-squamous NSCLC [ 6 ].…”