NICE Recommends Osimertinib for Advanced EGFR T790M Mutation-Positive NCSLC

It is indicated in adults whose disease has progressed after first-line treatment with an EGFR tyrosine kinase inhibitor

On 26 October 2016, the NICE issued evidence-based recommendations on osimertinib for treating locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC). It is recommended as an option for use within the Cancer Drugs Fund in adults whose disease has progressed after first-line treatment with an EGFR tyrosine kinase inhibitor (TKI) and if the conditions in the managed access agreement for osimertinib are followed. Next review is foreseen for March 2019 or when the results of the AURA3 trial are available, whichever is sooner.

This guidance is not intended to affect the position of patients whose treatment with osimertinib was started within the NHS before this technology appraisal guidance was published. Treatment of those patients may continue without change to whatever funding arrangements were in place for them before this guidance was published until they and their NHS clinician consider it appropriate to stop.

Osimertinib (Tagrisso, AstraZeneca) is a small-molecule inhibitor that targets the sensitising and T790M mutant forms of the EGFR-tyrosine kinase receptor.

Osimertinib has a conditional marketing authorisation for the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC. The marketing authorisation is conditional on the company submitting the clinical study report of the phase III AURA3 study comparing osimertinib with platinum-based doublet chemotherapy (expected June 2017).

The most common adverse reactions associated with osimertinib include diarrhoea, rash, dry skin, and a reduction in platelet count and some white blood cells.

Recommended dose and schedule is 80 mg taken orally once a day until disease progression or unacceptable toxicity.

The appraisal committee reviewed the data available on the clinical and cost effectiveness of osimertinib, having considered evidence on the nature of locally advanced or metastatic EGFR T790M mutation-positive NSCLC and the value placed on the benefits of osimertinib by people with the condition, those who represent them, and clinical experts. It also took into account the effective use of NHS resources.

The committee heard from the patient experts that EGFR mutation-positive NSCLC causes many distressing and debilitating symptoms, and typically has a poor prognosis. Even slight symptomatic improvements are very important for people with this condition, and even a small extension to life would be significant. The clinical and patient experts stated that people with the T790M mutation represent the minority of those with non-squamous NSCLC (between 0.5% and 6% at diagnosis). The committee heard from the experts that the availability of osimertinib could be a step change in the management of the condition, similar to the arrival of the original TKIs. It noted that in about 60% of people with EGFR mutation-positive NSCLC, their disease will become resistant to treatment with other TKIs because of T790M mutations. The clinical experts agreed that there will be fewer visits to hospital associated with osimertinib because it is better tolerated than other treatments, such as platinum-doublet chemotherapy, so an oral targeted therapy for this population is welcomed. The committee concluded that the availability of a new targeted treatment option with improved tolerability would be valuable for people with EGFR T790M mutation-positive NSCLC.

Price is 5,770.00 GBP per pack (30 tablets) of 80 mg tablets and 5,770.00 GBP per pack (30 tablets) of 40 mg tablets (excluding VAT). Treatment is continued until disease progression.

The pricing arrangement considered during guidance development was that the company (AstraZeneca) had agreed a patient access scheme with the Department of Health. This scheme would provide a simple discount to the list price of osimertinib with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme would not constitute an excessive administrative burden on the NHS. The managed access agreement agreed in September 2016 replaced the patient access scheme.