Abstract
168 Background: Variants in DPYD and UGT1A1 impact toxicities experienced by patients being treated with FOLFIRI+bev. Testing allows providers to preemptively adjust dosing, reducing the toxicity that patients experience. We assessed the cost-effectiveness of pre-treatment testing for variants in DPYD and UGT1A1 in patients with mCRC receiving FOLFIRI+bev. Methods: We developed a six-state Markov model to compare pre-treatment genetic testing to no testing. The genetic testing arm screened for UGT1A1 and DPYD using a multi-gene panel. Patients were dosed per proposed guidelines (Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group) and allowed dose reductions based on toxicity. In the no-test arm, patients received full doses of FOLFIRI+bev, and dose reductions based on toxicity. Costs included medications, clinic visits, and hospitalizations to treat the disease and adverse events, and were obtained from the literature, adjusted to 2019 $US. Quality-adjusted life years (QALYs) were used to assess effectiveness. We used a US health care system perspective with a 16 week horizon, the average length of time patients were exposed to FOLFIRI+bev in clinical trials. We conducted sensitivity analyses to determine the impact of uncertainty on outcomes. Results: Genetic testing cost $25,563, generating 0.21 QALYs. Standard of care cost $25,515, generating 0.20 QALYs. This resulted in an incremental cost-effectiveness ratio (ICER) of $4963 per QALY gained. Results were sensitive to costs of post-progression care, the probability of carrying UGT1A1 variants, and the impact of low-functioning DPYD variants on side effects. Conclusions: Pre-treatment testing for DPYD and UGT1A1 in patients receiving FOLFIRI+bev for mCRC is cost-effective, well below typical oncology ICERs of $50,000-100,000 per QALY. Further work is needed to characterize the impact of post-progression treatment and supportive care medications.
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