Abstract
Background
Adjuvant fluoropyrimidine-based chemotherapy substantially reduces recurrence and
mortality after resection of stage 3 colon cancer. While standard doses of 5-fluorouracil
and capecitabine are safe for most patients, the risk of severe toxicity is increased
for the approximately 6% of patients with dihydropyimidine dehydrogenase (DPD) deficiency
caused by pathogenic DPYD gene variants. Pre-treatment screening for pathogenic DPYD gene variants reduces severe toxicity but has not been widely adopted in the United
States.
Methods
We conducted a cost-effectiveness analysis of DPYD genotyping prior to fluoropyrimidine-based adjuvant chemotherapy for stage 3 colon
cancer, covering the c.1129-5923C>G (HapB3), c.1679T>G (*13), c.1905+1G>A (*2A), and
c.2846A>T gene variants. We used a Markov model with a 5-year horizon, taking a United
States healthcare perspective. Simulated patients with pathogenic DPYD gene variants received reduced-dose fluoropyrimidine chemotherapy. The primary outcome
was the incremental cost-effectiveness ratio (ICER) for DPYD genotyping.
Results
Compared with no screening for DPD deficiency, DPYD genotyping increased per-patient costs by $78 and improved survival by 0.0038 quality-adjusted
life years (QALYs), leading to an ICER of $20,506/QALY. In 1-way sensitivity analyses,
The ICER exceeded $50,000 per QALY when the cost of the DPYD genotyping assay was greater than $286. In probabilistic sensitivity analysis using
a willingness-to-pay threshold of $50,000/QALY DPYD genotyping was preferred to no screening in 96.2% of iterations.
Conclusion
Among patients receiving adjuvant chemotherapy for stage 3 colon cancer, screening
for DPD deficiency with DPYD genotyping is a cost-effective strategy for preventing infrequent but severe and
sometimes fatal toxicities of fluoropyrimidine chemotherapy.
Keywords
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Article Info
Publication History
Published online: May 11, 2022
Accepted:
May 6,
2022
Received in revised form:
April 29,
2022
Received:
February 7,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
