Cost-Effectiveness of UGT1A1*28 Genotyping in Preventing Severe Neutropenia Following FOLFIRI Therapy in Colorectal Cancer.

Abstract

PURPOSE: Functional polymorphisms of the UGT1A1 gene, particularly the UGT1A1*28 variant, are associated with the severity of the bone marrow suppression in patients with metastatic colorectal cancer receiving irinotecan. This study assesses the cost-effectiveness of screening for UGT1A1*28 polymorphism associated with primary prophylactic Granulocytes Colony Stimulating Factor in patients homozygous for the *28 allele. The effectiveness was estimated based on the number of neutropenia avoided. METHODS: We modelled a theoretical population treated with combined 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) for metastatic colorectal cancer. A decision tree simulated the health outcomes, measured by the prevalence of neutropenic events for two strategies, with or without UGT1A1 genotype screening. The model incorporated direct hospital costs and was validated with a sensitivity analysis. We calculated the cost-effectiveness ratio: CE=∆C / ∆E = "genotyping" cost – "no genotyping" cost / number of febrile neutropenia avoided. RESULTS: In the "genotyping strategy", the cost to avoid one febrile neutropenia event per 1000 patients treated was € 942.8 to € 1090.1. The sensitivity analysis showed a better CE ratio of € 733.4 to € 726.6 per febrile neutropenic event avoided.CONCLUSIONS: UGT1A1 genotype screening before irinotecan treatment is a cost-efficient strategy for the hospital. Systematic genotyping prior to chemotherapy, and administration of CSF in patients homozygotes for the *28 allele allow to avoid 91 febrile neutropenias at an acceptable cost.

Cost Evaluation of Irinotecan‐Related Toxicities Associated With the UGT1A1*28 Patient Genotype

“…Strategies for the use of the results of the UGT1A1*28 testing have been described elsewhere. In *28/*28 patients, they vary from dose reduction of irinotecan at first cycle with adjustment of dosing based upon toxicity, to exclusion of patients from treatment with irinotecan and administration of other equally effective regimens . From an economic point of view, our data suggests to focus not only on the *28/*28 patients but also on the *1/*28 patients, considering the observed increase in toxicity‐management costs also in this class of patients ( Table ).…”

“…Previously published studies in the field applied decision‐analytic models to simulated clinical and genetic data, using computational modeling for the definition of the *28 screening cost‐effectiveness, in the prevention of irinotecan‐related toxicities. They mostly considered severe neutropenia as the only toxic event related to *28 genotype, and impacting toxicity management costs.…”

“…To date, some computational cost-effectiveness studies, based on simulated clinical scenarios, [9][10][11][12] have provided suggestions for UGT1A1*28 test clinical utility, although clinical validation studies are warranted to confirm the transferability of this theoretical evidence into a real clinical setting.…”

Pharmacogenomics of Human Uridine Diphospho-Glucuronosyltransferases and Clinical Implications

“…Notably, some regulatory bodies, including the US Food and Drug Administration, have recommended that a reduced initial dose of irinotecan should be considered in patients homozygous for UGT1A1 * 28 to minimize drug exposure and risk of toxicities. Overall, there is a strong biological rationale and reproducible evidence linking the UGT1A1*28 allele and dose‐limiting toxicities, and a number of studies supporting the hypothesis that genotyping of the UGT1A1*28 allele before irinotecan administration in colorectal cancer patients would be cost effective 19 . This marker thus falls into the category of pharmacogenetic markers associated with chemotherapeutic drug‐related toxicity.…”

Individualized Medicine

“…Due to lump sum remuneration (remuneration according to the DRG system as well as the quarterly lump sum according to the general assessment standard for outpatient services) IM can appear to be disadvantageous, if through the process of stratification, costs cannot be cut. Currently, in the field of pharmacogenomics only, a few studies on potential savings to service providers have been published (You et al 2009;Pichereau et al 2011). Consequently, for a hospital or a medical practice there is a high level of uncertainty connected to a decision for or against the adoption of IM.…”