National Institute for Health and Care Excellence (NICE) has recommended tepotinib, which is approved for the treatment of adult patients in Great Britain with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations.

Tepotinib is the first and only oral MET inhibitor to be recommended for the treatment of adult patients with advanced NSCLC harbouring METex14 skipping alterations for use on the NHS in England, Wales and Northern Ireland. 

Interim funding via the Cancer Drugs Fund will enable reimbursement of tepotinib in England until NICE final guidance is published and funded after a 30-day mandatory period. In Northern Ireland, tepotinib was approved via the European Medicines Agency (EMA) marketing authorisation in February 2022 and access for eligible patients will be in line with this authorisation.

Dr Shobhit Baijal, Consultant Medical Oncologist, University Hospital Birmingham NHS Trust explains: “Existing treatment options for patients with METex14 skipping mutations have generally shown limited progression-free survival and overall survival benefits.

 Tepotinib is a new targeted therapy and the first MET inhibitor to be made available for eligible patients.  It is a significant step forward in the treatment of adult advanced NSCLC patients with METex14 skipping alterations and has demonstrated its clinical benefits for this aggressive type of lung cancer. Treatment involves identifying a genomic biomarker to be able to provide this new potential treatment option.”

NSCLCs with MET alterations are generally associated with poorer clinical prognosis compared to NSCLCs without MET alterations, with a lower median overall survival observed when compared to NSCLC patients without the alteration.

The presence of these genetic alterations has been recognised as an important therapeutic target for personalised treatment, which can be identified via a tissue sample. 

“It is excellent news to hear that NICE has approved tepotinib for people with non-small cell lung cancer and MET alterations. This is an aggressive type of lung cancer so we welcome any and all new treatments that could give patients a chance to live longer and live well with this disease.

It is vital all patients have access to more targeted treatments for their specific type of lung cancer and that they undergo genomic testing. That way, they can benefit from the new therapies, like tepotinib, that are now available to them,” said Paula Chadwick, Chief Executive, Roy Castle Lung Cancer Foundation.

Targeted treatments, like tepotinib, require genomic testing to determine which patients are eligible. To enable advanced genomic testing, the NHS is in the process of developing Genomic Laboratory Hubs (GLH) across the UK, which are equipped with novel technology to manage more complex tests that cannot be completed at other laboratory sites.

These hubs perform comprehensive genomic assessments on patients, providing detailed information about their cancer, allowing their clinician to select the most appropriate and targeted treatment available for them. 

The tests carried out in England are determined by the 2021/2022 National Genomic Test Directory, which is commissioned by the NHS; METex14 skipping is expected to be included in the forthcoming testing directory update.

Doina Ionescu, General Manager, Merck says: “We are committed to our vision for the future of medicine – moving away from a ‘one size fits all’ approach that is now the norm for many diseases to a focus on personalised medicines and the development of innovative targeted treatments, like tepotinib.

As the first therapy of its kind to be recommended by NICE, tepotinib has shown to help slow disease progression and prolong survival in patients with this gene mutation. Importantly, the NHS is also making progress in the screening of lung cancer patients with these types of specific gene mutations, helping to identify those patients who are most likely to benefit from this treatment.”

The pivotal clinical trial underpinning this NICE appraisal is the Phase II VISION study evaluating tepotinib as monotherapy in adult patients with advanced or metastatic NSCLC with METex14 skipping alterations, prospectively assessed by liquid biopsy or tissue biopsy.

The VISION study has demonstrated significant benefits for patients with advanced NSCLC with METex14 skipping enrolled by liquid biopsy or tissue biopsy.

In the VISION study, efficacy was evaluated in 275 patients and the study demonstrated an objective response rate, the primary outcome measure, by independent review of 49.1% (95% confidence interval [CI], 43.0-55.2) in the combined-biopsy group.

The median progression-free survival was 10.8 months (95% CI: 8.5-12.4), and the median overall survival was 19.7 months (95% CI: 15.6-22.1), with results consistent between previously untreated and previously treated patients.

These results are from a data cut-off date of February 2021.

Through the Medicines and Healthcare Products Regulatory Agency (MHRA) Early Access to Medicines Scheme (EAMS) and subsequent extensions to the scheme, eligible patients have already been initiated on treatment with tepotinib throughout the UK.

This means that these patients have been able to benefit from treatment prior to NICE approval and furthermore, many oncologists now have real-world clinical experience on how to prescribe tepotinib and manage patients with METex14 skipping mutations to optimise outcomes. Tepotinib is also under review by the Scottish Medicines Consortium (SMC) in Scotland and a decision is expected in Q2 2022.

Source: Merck