The Scottish Medicines Consortium recommends Merck’s TEPMETKO® (tepotinib) as the first oral MET inhibitor treatment option for advanced NSCLC adult patients with METex14 skipping alterations

Today Merck, a leading science and technology company, announced that following a resubmission to the Scottish Medicines Consortium (SMC), TEPMETKO^® (tepotinib), a targeted therapy licensed in Great Britain by the MHRA for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations, has now been recommended for use via NHS Scotland. This change was made following an initial decision by the SMC in June 2022 not to recommend tepotinib.1 The positive recommendation for tepotinib was published by the SMC on 16 January 2023.

The SMC’s decision makes tepotinib the first and only oral targeted MET inhibitor for adult patients with advanced NSCLC harbouring METex14 skipping mutations to be provided for routine use via NHS Scotland for eligible patients living in Scotland,¹ offering greater treatment choice that can help to improve patient outcomes. With this recommendation, there is now equal access to tepotinib across Great Britain, following the positive recommendation by the National Institute for Health and Care Excellence (NICE) on 14 April 2022, after which tepotinib became available via routine commissioning in England and Wales.[1]^,[2]^,[3] Tepotinib is also available in Northern Ireland, but this is in line with the European Medicines Agency marketing authorisation which differs slightly as it is indicated for the treatment of adult patients with advanced NSCLC harbouring alterations leading to METex14 skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.[4]

Dr Brian Clark, Consultant Clinical Oncologist, Beatson West of Scotland Cancer Centre explains: “Treatment options are limited for advanced NSCLC patients with METex14 skipping alterations and survival for this rare subtype of cancer remains poor in Scotland. As the first targeted therapy available in Scotland for this group of patients, tepotinib is changing the way we treat these aggressive types of cancers and we will hopefully start to see improvements in patient outcomes. Key to this will be the uptake of biomarker testing now that we have routine access on the NHS.”

NSCLC patients with METex14 mutations are associated with a poor clinical prognosis, with a lower median overall survival than NSCLC patients without the alteration.2^,3 Until now, there have been no treatment options available in Scotland to specifically target these alterations.¹ Standard of care includes immunotherapy and/or chemotherapy, but these have been associated with limited progression-free survival and overall survival benefits in patients with METex14 alterations.^1,[5]^,[6]^,[7]

Targeted treatments, like tepotinib, require genomic testing to determine which patients are eligible for treatment.^3,11 METex14 skipping alterations have been recognised as a therapeutic target and can be identified via a tissue sample, and also via liquid biopsy.⁶ To enable advanced genomic testing, the Scottish Genetics Laboratory Consortium works across four regional genetics centres in Aberdeen, Dundee, Edinburgh and Glasgow,[8] which are equipped with novel technology to manage more complex tests that cannot be completed at other local laboratory sites. To help improve access more widely in Scotland, there is ongoing work led by the Molecular Pathology Consortium that supports both decision-making on tests to be provided nationally (led by the Molecular Pathology Evaluation Panel [MPEP]) and on decisions regarding implementation of the recommended tests (led by the Molecular Pathology Steering Group [MPCSG]).[9]

Dr Stuart Hill, Medical Director, Merck UK & Ireland comments: “Tepotinib represents an important step forward in improving targeted treatment options that not only help to slow disease progression, but importantly may prolong survival in adult patients with advanced NSCLC harbouring METex14 gene mutations, where there is still significant opportunity to improve outcomes. At Merck we are striving for a future that focuses on personalised medicines, developing innovative and accessible targeted therapies to treat advanced cancers and improve patient outcomes. Therefore, we are delighted that the SMC recommendation means that eligible patients in Scotland can now access this first of its kind treatment.”

Data from the Phase II VISION study, which was submitted to the SMC, has demonstrated clinical benefits for patients with advanced NSCLC with METex14 skipping enrolled by liquid biopsy or tissue biopsy.^4,5 In the VISION study, efficacy and safety were evaluated in 313 patients and tepotinib demonstrated an objective response rate, the primary outcome measure, by independent review, of 50.8% (95% confidence interval [CI], 45.1-56.5) in the combined-biopsy group.⁵ The median progression-free survival was 11.2 months (95% CI: 9.5-13.8), and the median overall survival was 19.3 months (95% CI: 15.8-22.3).⁵ These results are from a data cut-off date of February 2022. The most common adverse events (≥10%) were peripheral oedema (66.5%), nausea (23.3%), diarrhoea (22.4%), blood creatinine increase (21.7%), decreased appetite (11.2%), alanine aminotransferase increase (13.1%) and hypoalbuminaemia (23.0%). Serious adverse events occurred in 49.8% of patients who received tepotinib (N=313),⁵ and the most common serious adverse events were pleural effusion (5.8%), pneumonia (5.1%), followed by peripheral oedema (3.2%), and dyspnoea (3.5%).[10]

References

[1] SMC. Tepmetko. Available at: https://www.scottishmedicines.org.uk/medicines-advice/tepotinib-tepmetko-resub-smc2535/ [Accessed January 2023]

[1] Tong JH et al. MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non-Small Cell Lung Carcinoma with Poor Prognosis. Clin Cancer Res. 2016;22:3048–3056.

[1] Santarpia M, et al. A narrative review of MET inhibitors in non-small cell lung cancer with MET exon 14 skipping mutations. Transl Lung Cancer Res. 2021;10(3):1536–1556.

[1] Paik PK et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020 May 29.

[1] Thomas M, et al. Tepotinib in patients with MET exon 14 skipping NSCLC: Primary analysis of the confirmatory VISION Cohort C. Presentation number OA03.05. Presented at the World Conference on Lung Cancer, August 6-9, 2022; Vienna, Austria.

[1] Shah R, et al. MET Exon 14 skipping alterations in NSCLC. Current understanding and therapeutic advances. Available at: https://touchoncology.com/lung-cancer/journal-articles/met-exon-14-skipping-alterations-in-nsclc-current-understanding-and-therapeutic-advances/. [Accessed December 2022]

[1] NICE. Technology Appraisal Guidance [TA789]. Tepotinib for treating advanced non-small-cell lung cancer with MET gene alterations. Implementation. Available at: https://www.nice.org.uk/guidance/ta789/chapter/4-Implementation. [Accessed December 2022].

[1] Department of Health. NICE - Endorsed Technology Appraisals 2022/2023. Available at: https://www.health-ni.gov.uk/articles/nice-endorsed-technology-appraisals-20222023. [Accessed December 2022].

[1] Department of Health, Social Services and Public Safety: NICE Technology Appraisals - Process for Endorsement, Implementation, Monitoring and Assurance in Northern Ireland. Available at: https://www.health-ni.gov.uk/sites/default/files/publications/dhssps/hsc-sqsd-2-13.pdf. [Accessed December 2022].

[1] European Medicines Agency. Tepmetko: EPAR – Product information. Available at: https://www.ema.europa.eu/en/documents/product-information/tepmetko-epar-product-information_en.pdf. [Accessed January 2023].

[1] Awad MM, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer. 2019;133:96–102.

[1] Sabari J, et al. PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers. Annals of Oncology. 2018;29(10):2085-2091

[1] SMC. Advice on new medicines. Available at: https://www.scottishmedicines.org.uk/media/6953/tepotinib-tepmetko-final-may-2022-amended-230622-for-website.pdf. [Accessed December 2022].

[1] NHS Scotland. Genetic and molecular pathology laboratories. Available at: https://www.nss.nhs.scot/specialist-healthcare/specialist-services/genetic-and-molecular-pathology-laboratories/. [Accessed December 2022].

[1] NHS Scotland. Molecular Pathology Consortium – Scottish Pathology Network. Available at: https://www.pathology.scot.nhs.uk/molecular-pathology-consortium/. [Accessed December 2022]

[1] Merck Data on File

[1] Electronic medicines compendium (emc). 2022. TEPMETKO 225 mg film-coated tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/12970/smpc#gref [Accessed December 2022]

[1] Cancer Research UK. Lung cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer.  [Accessed December 2022].

[1] Scot PHO. Public Health Information for Scotland. Lung Cancer: key points (2020 data). Available at: https://www.scotpho.org.uk/health-wellbeing-and-disease/cancer-lung/key-points/

[Accessed December 2022]

[1] Cancer Research UK. Early Diagnosis Data Hub. Available at: https://crukcancerintelligence.shinyapps.io/EarlyDiagnosis/. [Accessed December 2022].

[1] Royal College of Physicians. National Lung Cancer Audit annual report 2018. Available at: https://www.rcplondon.ac.uk/projects/outputs/nlca-annual-report-2018. [Accessed December 2022].

[1] MET Crusaders. What is MET? Available at: https://metcrusaders.org/what-is-met/ [Accessed December 2022]

[1] Socinski MA, et al. MET Exon 14 Skipping Mutations in Non–Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations. JCO Precision Oncology. 2021; No 5:653-63.

[1] Roth KG, et al. Prolonged survival and response to tepotinib in a non-small-cell lung cancer patient with brain metastases harboring MET exon 14 mutation: a research report. Cold Spring Harb Mol Case Stud. 2020;6(6):a005785.