South East GLH: Update on NTRK testing

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Specialised Commissioning and Health in Justice
NHS England and NHS Improvement (London)
133-155 Waterloo Road
London
SE1 8UG

16th November 2020

Dear Colleague,

Re: Entrectinib, larotrectinib and genomic testing for neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours.

I am writing to advise you of changes to the provision of NTRK gene fusion genomic testing concerning entrectinib and larotrectinib for treating NTRK fusion-positive solid tumours. The changes to genomic testing provision are outlined in annexe 1. Phase 2 of the NTRK gene fusions implementation plan means that from 6 November 2020 additional patient groups can be tested to see if they have NTRK fusion-positive solid tumours and eligible to receive entrectinib or larotrectinib.

NICE in their Technology Appraisal guidance TA644: Entrectinib for treating NTRK fusion-positive solid tumours (published on 12 August 2020 available at https://www.nice.org.uk/guidance/ta644 ) have stated that:

Entrectinib is recommended for use within the Cancer Drugs Fund as an option for treating neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours in adults and children 12 years and older if:

• the disease is locally advanced or metastatic or surgery could cause severe health problems and
• they have not had an NTRK-inhibitor before and
• they have no satisfactory treatment options.

NICE in their Technology Appraisal guidance TA630: Larotrectinib for treating NTRK fusion-positive solid tumours (published on 27 May 2020 available at https://www.nice.org.uk/guidance/ta630 ) have stated that:

Larotrectinib is recommended for use within the Cancer Drugs Fund as an option for treating neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours in adults and children if:

• the disease is locally advanced or metastatic or surgery could cause severe health problems and
• they have no satisfactory treatment options.

Entrectinib and larotrectinib are both available via the Cancer Drugs Fund (CDF) in line with these recommendations and according to a set of treatment criteria which translates the NICE recommendation into a clinical guide as to use in practice. These treatment criteria can be found on the national CDF list at https://www.england.nhs.uk/cancer/cdf/cancer-drugs-fund-list/ or on the application form(s) on the Blueteq site.

Entrectinib and larotrectinib are available via the Cancer Drugs Fund (CDF) under the terms of the managed access agreement (MAA) and commercial access agreement (CAA), until NICE reviews this indication.

In addition:

• The MAA incorporates a commercial in confidence CAA which includes a PAS applicable across all indications in use in the NHS. Trusts must ensure that they are purchasing entrectinib and larotrectinib at the agreed PAS discounted price. This discounted price will be applied automatically at point of invoice.
• Trusts must ensure that only invoices for the drug procurement costs of entrectinib in this indication are directed to the CDF and that they are also submitting complete and accurate information via the CDF minimum dataset (MDS).
• In line with the terms and conditions included in the NHS Standard Contract and as per the agreement that Cancer Services are commissioned with Trusts, Schedule 6a Reporting Requirements for drugs will apply. Payment of Trust invoices will be contingent on the completion of the MDS record and this information being made available in a timely way.
• Trusts must ensure they are registering entrectinib and larotrectinib use on SACT. The SACT dataset is a mandated dataset as part of the Health and Social Care Information Standards. This is listed as a Schedule 6 national information requirement within the NHS Standard Contract.
• Patients must be registered via Blueteq (ENT1a plus ENT1b and LAR1a plus LAR1b ) and meet the clinical criteria on the registration forms.
Payment of Trust invoices will be contingent on Blueteq registration, the full SACT and CDF MDS record applicable to the drug being completed and this information being made available in a timely way.
• Trusts must ensure that local governance aspects (e.g. technical issues, education & training, patient information) have been identified and addressed for all staff groups (as appropriate) in order to permit the safe delivery of this therapy.

Trusts should refer to the CAP portal for further information on the PAS price. The CAP portal is available at https://nhsengland.sharefile.eu/Authentication/Login

London Trusts that are recognised centres for solid tumours are:

Barking Havering and Redbridge University Hospitals NHS Trust
Barts Health NHS Trust
Chelsea and Westminster Hospital NHS Foundation Trust
Guy’s and St Thomas’ NHS Foundation Trust
Homerton University Hospital NHS Foundation Trust
Imperial College Healthcare NHS Trust
King’s College Hospital NHS Foundation Trust
Lewisham and Greenwich NHS Trust
London North West Healthcare
North Middlesex University Hospital NHS Trust
Royal Free London NHS Foundation Trust
St George’s Healthcare NHS Trust
The Royal Marsden NHS Foundation Trust
The Whittington Hospital NHS Trust
University College London Hospitals NHS Foundation Trust

The two London Principal Treatment Centres (PTCs) for children and Teenagers/Young Adults (TYA) with cancer, which are each recognised as joint PTCs are:

Great Ormond Street Hospital with University College London Hospital
The Royal Marsden Hospital with St George’s Hospital.

I would be grateful if you could cascade this information to relevant clinical teams within your organisation to support the consistent adoption of the policy nationally.

If you have any queries regarding this guidance and it relates to a specific medicine, please liaise in the first instance with Trusts NHS England and NHS Improvement (NHSE/I) Clinical Commissioning Pharmacist (CCP) who can escalate to the Specialised Commissioning Pharmacy team for further clarification if appropriate. If you do not have a CCP please refer all queries to the Specialised Commissioning Pharmacy team for further review.

Yours sincerely,

Mark Turner

Director of Commissioning

Annex 1 – Genomic testing for NTRK gene fusions implementation plan

1. Determining eligibility for entrectinib relies on detecting the presence of the NTRK gene fusion via a genomic test. The genomic testing will be undertaken by the NHS Genomics Laboratory Hubs (GLHs). The aim is to achieve a testing rate of 30,000 patients per year by the end of 2020/21, which would capture all those solid tumour patients who were potentially eligible for the drugs at the point at which standard therapies had failed.

2. However, currently due to the impact of the COVID-19 pandemic the NHS GLHs have a reduced testing capacity due to the redeployment of staff and equipment to support COVID-19 testing. The deployment has resulted in the slow down or suspension of developmental work to establish NTRK testing capability and reduced testing capacity where development work had already been completed.

3. A phased implementation plan will be implemented to utilise the available testing capacity where it will have the most impact.

4. Phase 1 of testing was implemented on 21st April 2020, delivered by four GLHs on behalf of the whole country. Table 1 outlines the patients who are eligible for testing in phase 1.

5. Due to additional testing capacity, phase 2 of testing will be implemented from 6th November 2020. Table 2 outlines the patients who are eligible for testing in phase 2. Testing will be delivered by five GLHs on behalf of the whole country. Table 3 outlines the testing arrangements for phase 2.

Table 1: detailed testing plan for phase 1
(Note entrectinib is only funded for children 12 years and older so not all testing groups below will apply to use of entrectinib.)

 Testing group
1Four cancer in which NTRK gene fusion incidence is very high (>90%):
– Infantile fibrosarcoma
– Congenital mesoblastic nephroma
– Mammary-variant salivary gland cancer
– Secretory breast cancer
2Three cancers in which NTRK gene fusion incidence is between 5 and 25%:
– Gastro-intestinal tumours (GISTs)
– Thyroid cancers
– Spitzoid neoplasms
3Children (0-16) with solid tumours being treated in Principal Treatment Centres
4Teenagers (16-18) with solid tumours
5Young adults (18-25) with solid tumours

Table 2: detailed testing plan for phase 2
(Note entrectinib is only funded for children 12 years and older so not all testing groups below will apply to use of entrectinib.)

 Testing group
1All patients eligible for testing via phase 1 (see table 1)
2Solid tumour patients with metastatic/locally advanced disease, or where surgical resection is likely to result in severe morbidity, for whom standard therapies have failed, or none are available, and are fit for further treatment

Table 3: genomic testing laboratories for phase 2

Testing GLHTesting laboratory in GLHKey laboratory contactGeography covered
Yorkshire and North East GLHNewcastle upon Tyne Hospitals NHS Foundation Trustnuth.cancer.genomics@nhs.netYorkshire and North East GLH
North West GLHManchester University Hospitals NHS Foundation TrustMft.pharmaco.geneticsrequests@nhs.netNorth West GLH
West Midlands, Oxford and Wessex GLHBirmingham Women’s and Children’s NHS Foundation Trustbwc.RGLMolecularPathologyTeam@nhs.net;

Yvonne Wallis y.wallis@nhs.net
West Midlands, Oxford and Wessex GLH
London North GLHThe Royal Marsden NHS Foundation Trustrmh-tr.moleculardiagnostics@nhs.netLondon North GLH, London South GLH and East of England GLH
South West GLHBristol Genetics Laboratorynbn-tr.geneticsenquiries@nhs.netSouth West GLH

6. The histopathology laboratory should use the genomic testing laboratory’s Test Request Form and send a formalin-fixed paraffin-embedded (FFPE) tumour sample directly to the genomic testing laboratory designated to perform the testing on behalf of that geography as outlined in table 2. The testing laboratory will perform the extraction, testing, interpretation and report the result back to the referring oncologist.

7. NHS England and NHS Improvement will continue to work with the Genomic Laboratory Hubs to agree a timeline for the expansion of genomic testing capacity.

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With any Whole Genome Sequencing (WGS) test ordered, a Record of Discussion (RoD) form will also need to be submitted. This document is to record the patient’s consent for genomic testing and their choice on taking part in research. Guidance on the patient choice conversation can be found here
 
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