Fluorpyrimidine-based chemotherapy drugs, such as 5-fluorouracil (5FU) and capecitabine, are approved and have long been used for the treatment of primary and advanced solid tumours such as colorectal, esophageal, stomach, pancreatic, head and neck, and breast. Usually cancer patients that are treated with fluorpyrimidine-based chemotherapy drugs tolerate the therapy well. However, 5-30% of these patients might develop severe or mild adverse reactions due to the presence of genetic mutations that cause dihydropyrimidine dehydrogenase (DPD) deficiency. DPD is the main enzyme that degrades up to 90% of the administered chemotherapy drugs and its deficiency leads to poor metabolism of the drugs, and thus, adverse reactions. Testing with genetic tests can help identify the patients that have a genetic mutation causing DPD deficiency, and thus allow clinicians to carefully monitor patients’ therapy, reduce the administered dose or switch to other treatment when necessary. Genetic testing prior to initiation of 5FU/capecitabine therapy can help reduce the number of adverse reactions experienced by patients, and thus improve patient safety. ToxNav is a genetic test that assesses 19 genetic variants identify the patients that have a genetic mutation causing DPD deficiency. This allows to personalise their treatment with chemotherapy on the basis of individual patient characteristics. Thus, adverse reactions could be avoided which would have a positive impact on patients’ safety, quality of life and survival. From an economic point of view, healthcare expenditures for managing adverse reactions could be potentially reduced or avoided. The economic model will focus on patients with metastatic breast cancer. The model will compare a clinical pathway that includes testing with ToxNav to standard care pathway in which patients are not tested. Patients tested with ToxNav will have their treatment personalised on the basis of the outcome of the genetic test. All patients in the standard care pathway will receive standard chemotherapy. The model will evaluate the impact of adverse reactions on patients’ quality of life and survival, as well as on healthcare costs, and follow the cohort of patients through their potential progression to advanced disease, or death from metastatic breast cancer or other causes. The model will evaluate the quality-adjusted life years and healthcare costs accrued by patients in the two clinical pathways, and thus, assess the cost-effectiveness of testing with ToxNav over standard care.
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