Cost-utility analysis and cross-country comparison of pharmacogenomics-guided treatment in colorectal cancer patients participating in the U-PGx PREPARE study

Objectives: A cost-utility analysis was conducted to evaluate pharmacogenomic (PGx)-guided treatment compared to the standard-of-care intervention among patients diagnosed with colorectal cancer (CRC) in Italy. Methods: Data derived from a prospective, open-label, block randomized clinical trial, as a part of the largest PGx study worldwide (355 patients in both arms) were used. Mortality was used as the primary health outcome to estimate life years (LYs) gained in treatment arms within a survival analysis context. PGx-guided treatment was based on established drug-gene interactions between capecitabine, 5-fluorouracil and irinotecan with DPYD and/ or UGT1A1 genomic variants. Utility values for the calculation of Quality Adjusted Life Year (QALY) was based on Visual Analog Scale (VAS) score. Missing data were imputed via the Multiple Imputation method and linear interpolation, when possible, while censored cost data were corrected via the Replace-From-The-Right algorithm. The Incremental Cost-Effectiveness Ratio (ICER) was calculated for QALYs. Raw data were bootstrapped 5000 times in order to produce 95% Confidence Intervals based on non-parametric percentile method and to construct a cost-effectiveness acceptability curve. Cost differences for study groups were investigated via a generalized linear regression model analysis. Total therapy cost per patient reflected all resources expended in the management of any adverse events, including medications, diagnostics tests, devices, surgeries, the utilization of intensive care units, and wards. Results: The total cost of the study arm was estimated at euro380 (similar to US$416; 95%CI: 195-596) compared to euro565 (similar to US$655; 95%CI: 340-724) of control arm while the mean survival in study arm was estimated at 1.58 (+0.25) LYs vs 1.50 (+0.26) (Log Rank test, X2 = 4.219, df=1, p-value=0.04). No statistically significant difference was found in QALYs. ICER was estimated at euro13418 (similar to US$14695) per QALY, while the acceptability curve indicated that when the willingness-to-pay was under euro5000 (similar to US$5476), the probability of PGx being cost-effective overcame 70%. The most frequent adverse drug event in both groups was neutropenia of severity grade 3 and 4, accounting for 82.6% of total events in the study arm and 65.0% in the control arm. Apart from study arm, smoking status, Body-Mass-Index and Cumulative Actionability were also significant predictors of total cost. Subgroup analysis conducted in actionable patients (7.9% of total patients) indicated that PGx-guided treatment was a dominant option over its comparator with a probability greater than 92%. In addition, a critical literature review was conducted, and these findings are in line with those reported in other European countries. Conclusion: PGx-guided treatment strategy may represent a cost-saving option compared to the existing conventional therapeutic approach for colorectal cancer patient management in the National Health Service of Italy.