1204P - Real-world utility of whole genome sequencing for patients with cancer: Evaluation of a regional implementation of the 100,000 genomes project

Background

Comprehensive molecular profiling is essential for personalised cancer care. In the United Kingdom, Genomics England partners with the National Health Service to provide whole-genome sequencing (WGS). The 100,000 Genomes Project established infrastructures to incorporate WGS into clinical practice. However, the real-world utility of whole genome sequencing in adult cancer patients is poorly described.

Methods

The 100,000 Genome Project is a national prospective cohort study, which sought to sequence 100,000 whole genomes from patients with cancers or rare diseases. This is a retrospective evaluation of data collated during the 100,000 Genome Project for patients with cancers recruited by the West Midlands Genomic Medicine Centre. Actionable genes are defined by the GenomOncology Knowledge Management System as genes with reported therapeutic, prognostic or clinical trial associations. The presented work evaluates the clinical utility of WGS by assessing the variants identified, GTAB recommendations, and whether recommendations altered clinical practice.

Results

4851 participants were included. A third of patients had no sample or sample failed quality control (1451/4851; 29.9%). 37.4% of patients (1816/4851) were clinically excluded (including due to death or poor fitness) before Genomics Tumour Advisory Board (GTAB) discussion. For those with successful sequencing (24.4%; 1183/4851), 7 in 10 (846/1183; 71.5%) had reported potentially actionable variants, of whom 428/846 (50.6%) had recommendations made. One in 12 participants (8.6%; 416/4851) had GTAB recommendations, the majority being additional treatments or clinical trials (60.6%; 252/416). Clinical exclusion rates and the availability of GTAB recommendations varied between cancer types (p<0.0001). At the last follow up, only a small proportion of patients had therapeutic recommendations followed, representing 5.2% of all recommendations (13/252).

Conclusions

The 100,000 Genomes Project has established essential infrastructure and regional experience to deliver WGS. The majority had potentially actionable variants. Ensuring GTAB recommendations are followed will maximize benefits for patients.

Clinical trial identification

The current work is a retrospective analysis of patients enrolled in the 100,000 genome project in the West Midlands. All data analysed was routinely collected. The 100,000 genome project was approved by the HRA Committee East of England Cambridge South (REC Ref 14/EE/1112).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Middleton: Financial Interests, Personal, Advisory Board: BMS, Roche, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: BMS, Roche, Boehringer Ingelheim, AstraZeneca, Servier, Takeda; Financial Interests, Institutional, Research Grant, Funding for organoids: AstraZeneca; Financial Interests, Institutional, Research Grant, Clinical Trial Funding: BMS, MSD. A.D. Beggs: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor, Laboratory support and consultancy fees: Illumina Inc, Oxford Nanopre. All other authors have declared no conflicts of interest.