ToxNav germline genetic testing and PROMinet digital mobile application toxicity monitoring: Results of a prospective single‐center clinical utility study—PRECISE study

Abstract

IntroductionIn this study (PRECISE), we assess the clinical utility of a germline DNA sequencing‐based test (ToxNav) for mutations in DPYD and ENOSF1 genes to alter clinician‐prescribed fluoropyrimidine doses and the use of a digital application (PROMinet) to record patient‐reported chemotherapy toxicity.Materials and methodsAdult patients with a histological diagnosis of colorectal cancer (CRC) who consented to fluoropyrimidine‐based chemotherapy were recruited prospectively and given a digital application to monitor and record associated toxicities. Patient samples were analyzed for 18 germline coding variants in DPYD and 1 ENOSF1 variant.ResultsGenetic testing was performed for 60 patients and identified one patient at increased risk of fluoropyrimidine‐based toxicities. Uptake of genetic testing was high and results were available on average 17 days from initial clinical encounter. Patient‐reported chemotherapy toxicity identified differences in 5‐fluorouracil vs capecitabine regime profiles and identified profiles associated with subsequent need for chemotherapy dose reduction and hospital admission.DiscussionThe PRECISE clinical trial demonstrated that a germline DNA sequencing‐based test can provide clinically relevant information to alter clinicians' fluoropyrimidine prescription. The study also obtained high volume, high granularity patient‐reported toxicity data that might allow the improvement and personalization of chemotherapy management.

An Evaluation of the Diagnostic Accuracy of a Panel of Variants in DPYD and a Single Variant in ENOSF1 for Predicting Common Capecitabine Related Toxicities

“…In many countries there is still a lack of recommended systematic testing. Routine testing for the four variants with high level evidence highlighted by CPIC and DPWG is now recommended in the UK and the PRECISE study [ 22 ] demonstrated that a test including 3 of these variants as part of a larger panel (no marker for HapB3 included) provided clinically relevant information to clinicians prior to their prescribing chemotherapy.…”

Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients

“…In this study, we used the extended ToxNav® (Oxford Cancer Biomarkers) panel that included three of the four CPIC alleles as the PRECISE study had shown that the rs56038477/rs75017182 HAPB3 allele indicated 75% enzyme activity and normal dose of 5-FU/Capecitabine was recomended [ 18 ] (more details are provided in Appendix B). In addition, ToxNav® included 15 more variants associated with DPYD function and one allele of the ENOSF1 gene [ 11 ].…”