Cost implications of reactive versus prospective testing for dihydropyrimidine dehydrogenase (DPD) deficiency in patients with colorectal cancer.

Abstract

3627 Background: DPD is an enzyme encoded by the DPYD gene involved in the metabolism of the chemotherapy drug 5-fluorouracil (5FU) and the oral 5FU prodrug capecitabine. Patients (pts) with DPYD mutations are at risk of severe toxicities from standard dose 5FU, although they may safely receive lower dose therapy with careful monitoring and dose escalation. Methods: In this retrospective study we identified all pts starting 5FU-based chemotherapy for colorectal cancer (CRC) at our institution between Jan 1 2010 and Dec 31 2012. During this time DPD testing was usually performed in a reactive manner, typically for pts experiencing severe toxicities. We reviewed the charts of pts who tested positive for DPYD mutations and assessed the financial implications of their hospitalizations with toxicity. These costs were compared to the costs which would have incurred if all pts starting such therapy had been proactively tested. Results: A total of 134 pts started first-line 5FU-based chemotherapy for CRC over the study period, 66 in the adjuvant setting and 68 for metastatic disease. 31 pts had DPYD mutation testing performed. 6 tests (19% of those tested, 4.5% of the total population) revealed heterozygote DPYD mutations. 5 pts had already experienced severe treatment-related toxicity resulting in cessation of therapy, while one was tested prospectively and received chemotherapy with dose reduction ab initio. The total cost related to hospitalization with toxicity for these 5 pts was €155,083. At €177 per test, the cost to prospectively test all pts starting first-line 5FU-based therapy over the time period would have been €23,718 representing a saving of €131,365 through avoiding these admissions alone. 4 pts who tested positive for DPYD mutations were receiving adjuvant therapy and none restarted therapy following severe toxicity early in their therapy. 2 pts subsequently relapsed with metastatic disease. Conclusions: Prospective testing for DPYD mutations in pts with CRC starting 5FU-based therapy for the first time represents a considerable cost-saving opportunity, in addition to potentially avoiding prolonged hospitalization and morbidity for a sizeable minority of pts.

Prospective DPYD genotyping to reduce the risk of fluoropyrimidine-induced severe toxicity: Ready for prime time

“…Five patients carried a variant and were admitted to the ICU due to toxicity. The costs of hospital admission (V155,083) were much higher than the screening costs of all patients starting with fluoropyrimidine therapy for CRC during the study period (V26,800) [53]. Another retrospective study of 48 patients shows cost-effectiveness with DPYD screening costs for four variants being almost nine times lower than hospital admissions of four patients (£1,776 versus £15,525; approximately V2,500 versus V21,500) [58].…”

Clinical Implementation of Germ Line Cancer Pharmacogenetic Variants During the Next-Generation Sequencing Era

“…Of note, a cost implications analysis of reactive vs. prospective DPYD genotyping in 134 CRC patients receiving fluorouracil-based therapy revealed the potential for a total cost saving of €131,165 (~$173,000) through avoiding five hospitalizations by preemptively genotyping the patients. 54 Similarly, a cost-effectiveness analysis of screening for KRAS and BRAF mutations in CRC patients to direct treatment with cetuximab as compared with the base strategy (no anti-epidermal growth factor receptor therapy) reported an incremental cost-effectiveness ratio of ~ $650,000 per additional year of life; the addition of KRAS testing saves ~ $7,500 per patient. 55 A critical and systematic review of the cost-effectiveness of pharmacogenetics revealed that one of the most common biomarkers evaluated was TPMT; these studies were focused on a number of indications for thiopurines, including cancer, inflammatory bowel disease, Crohn's disease, and rheumatoid arthritis.…”

“…Few studies have evaluated the cost‐effectiveness of cancer pharmacogenetics in practice. Of note, a cost implications analysis of reactive vs. prospective DPYD genotyping in 134 CRC patients receiving fluorouracil‐based therapy revealed the potential for a total cost saving of €131,165 (~$173,000) through avoiding five hospitalizations by preemptively genotyping the patients 54 . Similarly, a cost‐effectiveness analysis of screening for KRAS and BRAF mutations in CRC patients to direct treatment with cetuximab as compared with the base strategy (no anti–epidermal growth factor receptor therapy) reported an incremental cost‐effectiveness ratio of ~ $650,000 per additional year of life; the addition of KRAS testing saves ~ $7,500 per patient 55 .…”