Reporting of additional genomic targets in solid tumours to support patient access to emerging treatments and clinical trials.

Background

NHS England have recently set out a series of steps for GLHs to include additional clinical trials targets in the molecular reporting of solid cancers. The first of these steps (step 1) includes the addition of a small number of genes to our NGS panel reports.

This communication describes the approach the NEY GLH has taken to make these changes. Please contact [email protected] for further information. A further communication will be issued in 2025 on the next NHSE stepwise changes – to include further increases in the number of clinical trials gene targets tested/reported.

Changes from November 2024

For solid tumour samples received after Monday 25th November 2024, we will commence analysis and reporting of the Step 1 additional clinical trials targets for the majority of solid tumour samples WHERE THEY ARE INCLUDED IN THE PANEL BEING TESTED. This will be for 5 genes associated with the DETERMINE clinical trial (Cancer Clinical Trial | DETERMINE Precision Medicine (cancerresearchuk.org)). These genes are included in the National Genomic Test Directory v10 dated 23rd October 2024, which sets out the targets under 2 new columns entitled “Target Gene(s) Clinical trials” and “Further Eligibility Criteria Clinical trials targets only”.

What additional targets will we report from our gene panels?

The genes and variant types are as follows: BRAF (small variants and fusions), ERBB2 (small variants and amplifications), MET (amplifications, exon 14 skipping variants and fusions), ALK (fusions), and ROS1 (fusions). We will report the following targets from our current NGS panels:

    1. Genexus panel (small variants, copy number changes and gene fusions) – BRAF (small variants and fusions), ERBB2 (small variants only), MET (amplifications, exon14 skipping variants and fusions), ALK (fusions), and ROS1 (fusions). We will not be reporting on ERBB2 amplification status
    2. TSO500 DNA panel (small variants) – BRAF small variants and ERBB2 small variants. We will not be reporting on ERBB2 or MET amplification status, and will not be reporting on MET exon 14 skipping status
    3. TSO500 RNA panel (gene fusions) – BRAF fusions, MET fusions, ALK fusions, and ROS1 fusions. We will not be reporting on MET exon 14 skipping status
    4. RNA fusion panel (gene fusions) – BRAF fusions, ALK fusions, and ROS1 fusions. We will not be reporting on MET fusions or on MET exon 14 skipping status
    5. Paediatric DNA panel (small variants) – BRAF and ERBB2 small variants. We will not be reporting on ERBB2 or MET amplification status, and will not be reporting on MET exon 14 skipping status

What will be reported on clinical trials targets?

Reports will include the known, likely oncogenic variants detected in the step one targets on the routine genomic report but will not include any further clinical interpretation of these.

Support for clinical teams

We recognise that the addition of genomic variants on a patient’s report beyond those required for standard of care treatment may cause concern for some clinical teams. We therefore recommend that additional gene variants COULD be discussed at our regional Genomic Tumour Advisory Board (GTAB) meetings – see button below. These can help with interpretation and provision of information about possible appropriate clinical trials or treatments. There are also several resources available for all oncologists, including the ECMC trial finder (https://www.ecmcnetwork.org.uk/ec-trial-finder).

You can find the GTAB Referral form and more information here

GTAB meetings

Our GLH currently runs GTAB meetings for adult cancers (alternate Tuesdays 12-1pm), paediatric/TYA cancers (alternate Tuesdays 4-5pm), and CNS tumours (alternate Wednesdays 2-3pm). A request to have the genomic results of a patient discussed at a GTAB can be made by contacting [email protected], and submitting a short form outlining patient details and reason for the request (see “NEY GLH GTAB form for solid tumour molecular result review” on our website).  Notification will then be made of when the next appropriate GTAB date will be, and the requester will be encouraged to attend and present the patient’s details for discussion.

Who to contact for further information

For any further questions, please contact your local genomics laboratory.