SEMINAR :: Examining the Cost-Effectiveness of Pharmacogenomic Strategies to Individualize Care for Cancer Patients
The broad availability of genetic information arising from the Human Genome Project promises to bring new modalities for testing and treatment to oncology. Advances in cancer cell biology and genetics now permit the detection of individuals with hereditary predisposition to disease, the development of gene-based drug therapies, and the individualization of drug therapy based on a patient's genetics. Pharmacogenomics refers to a spectrum of approaches to explore the association of genetic variation at any locus with drug activity or toxicity. In contrast to most drugs outside of oncology, anticancer drugs are often customized based on individual patient characteristics, such as a patient's body surface area. Despite this individualized dosing, there is great heterogeneity in the ways that patients respond to medications, in terms of both toxicity and treatment efficacy. Thus, drug dosage and selection are adjusted modified once therapy has begun based on the severity of ensuing drug toxicities and efficacy. Genetic polymorphisms in drug-metabolizing enzymes, transporters, and receptors, and in cancer cells may explain some of the inter-individual differences in the efficacy and toxicity of chemotherapy, and suggest the need for individualized therapy based on genetic information. However, the economic implications of pharmacogenomic testing prior to administering chemotherapy remain unclear. We have investigated the general principles underlying the potential for pharmacogenomic treatment strategies to become cost-effective, and are examining the cost-effectiveness particular pharmacogenetic and pharmacogenomic interventions. I will discuss a Markov model that examines the cost-effectiveness of screening children with acute lymphoblastic leukemia (ALL) for thiopurine methyltransferase (TPMT) deficiency prior to instituting 2.5 years of maintenance therapy with 6-mercaptopurine (6-MP). Children with TPMT deficiency (0.3% US population) treated with 6-MP experience severe bone marrow suppression and may die, but a simple, prospective dose reduction can prevent this effect. The model was used to compare the costs and quality-adjusted survival for children managed with pharmacogenomic testing versus those receiving conventionally-dosed 6-MP. I will also describe studies to assess the incremental cost-effectiveness of DPD genotyping prior to initiation of 5-FU therapy and UGT1A1 genotyping prior to initiation of irinotecan therapy for patients with colorectal cancer, and related work in oncology informatics to link utility-based measures of outcome to an existing database containing clinical, administrative, pharmacy, and genetic data. This enhanced database will facilitate future cost-utility studies of pharmacogenomics.
References Bala MV, Zarkin GA. Pharmacogenomics and the evolution of healthcare : is it time for cost-effectiveness analysis at the individual level? Pharmacoeconomics. 2004;22(8):495-8. Flowers CR, Veenstra D. The role of cost-effectiveness analysis in the era of pharmacogenomics. Pharmacoeconomics. 2004;22(8):481-93. Danzon P, Towse A. The economics of gene therapy and of pharmacogenetics. Value Health. 2002 Jan-Feb;5(1):5-13.
Dr. Christopher Flowers, MD, is an Assistant Professor in Hematology and Oncology and the Clinical Director for Oncology Informatics Program at the Winship Cancer Institute, Emory University School of Medicine