Background

Upfront molecular stratification of cancer patients to experimental early phase clinical trials, using solid tumour profiling, can improve patient outcomes and drug development success. Liquid circulating tumour deoxyribonucleic acid (ctDNA) assays, such as FoundationOne Liquid (FOL), can also provide genomic tumour profiles and have the advantages of being less invasive, able to detect tumour heterogeneity and suitable for serial testing. FOL is FDA approved as a companion diagnostic for several indications. The role of ctDNA assays in matching patients to early phase clinical trials remains to be determined. We sought to investigate the clinical utility of FOL testing in the Newcastle Experimental Cancer Medicine Centre (ECMC) cohort.

Method

Retrospective data collection of all patients referred for early phase clinical trials and undergoing FOL testing between 12/12/2018 and 10/12/2020 at the Newcastle ECMC. Data collected from electronic notes included: demographics, FOL test results, subsequent treatment and trial enrolment and survival. Statistical analysis was performed using GraphPad Prism.

Results

144 FOL tests were performed in 131 patients during the two-year period. The most common cancers represented were lung, breast and colorectal. The median patient age was 62 years old. Of the 144 tests, 118 (81.9%) detected at least one genomic finding. 103 tests (71.5%) were deemed ‘actionable’ as they detected genomic findings that were targeted in clinical trials. 21 tests (14.6%) led to patients being matched to available trial slots and seven tests (4.9%) resulted in patients starting a matched trial. The FOL test failure rate was low at 8.3%.

Conclusion

ctDNA assays have huge potential as an alternative to solid biopsies in matching patients to trials and assessing response to experimental treatments. In our Newcastle cohort, the major loss of clinical utility for FOL was in the lack of a local or UK-wide, tumour site focused trial slot. Further work is needed to improve access to targeted early phase trials and increase understanding within the UK early phase trial community about how to use FOL testing.

Impact statement

This work supports the use of ctDNA assays in matching patients to targeted early phase clinical trials which may improve patient outcomes and drug development success.