On 8 August 2018, the NICE released Technology appraisal guidance [TA535] on lenvatinib (Lenvima, Eisai) and sorafenib (Nexavar, Bayer) for progressive, locally advanced or metastatic differentiated thyroid cancer in adults who have had radioactive iodine.
Lenvatinib and sorafenib are recommended as options for treating progressive, locally advanced or metastatic differentiated thyroid cancer (papillary, follicular or Hürthle cell) in adults whose disease does not respond to radioactive iodine, only if:
- they have not had a tyrosine kinase inhibitor before or
- they have had to stop taking a tyrosine kinase inhibitor within 3 months of starting it because of toxicity (specifically, toxicity that cannot be managed by dose delay or dose modification).
Lenvatinib and sorafenib are recommended only if the companies provide them according to the commercial agreements.
This recommendation is not intended to affect treatment with lenvatinib or sorafenib that was started in the NHS before this guidance was published. Patients having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.
Tyrosine kinase inhibitors, lenvatinib and sorafenib are the only treatment options for progressive, locally advanced or metastatic differentiated thyroid cancer after surgery and radioactive iodine. For patients who cannot have lenvatinib or sorafenib, best supportive care is the only option.
Dosage of lenvatinib in the marketing authorisations is 24 mg (2×10 mg capsules and 1×4 mg capsule) once daily and for sorafenib 400 mg (2×200 mg tablets) twice daily (equivalent to a total daily dose of 800 mg). Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs.
Clinical trial evidence shows that lenvatinib and sorafenib are both effective in delaying disease progression, but there is a higher response rate with lenvatinib and it may delay progression for longer. Clinical expert advice is that this response is associated with an improvement in symptoms, which is valued by patients. Lenvatinib and sorafenib also increase the overall survival, but it is uncertain by how long.
The cost-effectiveness estimates are higher than what NICE normally considers acceptable, and lenvatinib and sorafenib do not meet NICE's end-of-life criteria. But the treatments do increase length of life and there are no other treatments available for the condition. Also, the cost-effectiveness estimates do not capture the benefits of patients having a response to treatment, that is, an improvement in symptoms.
Taking all this into account, lenvatinib and sorafenib are recommended as treatment options for differentiated thyroid cancer after radioactive iodine. However, they are recommended only for patients who have not had tyrosine kinase inhibitors before, or who have to stop them early because of tolerability (specifically, toxicity that cannot be managed by dose delay or dose modification). This is because there is not enough clinical evidence and no cost-effectiveness evidence to determine whether the treatments are effective when used sequentially.
The price of lenvatinib is 1,437 GBP per 30×10 mg pack and per 30×4 mg pack (excluding VAT; British national formulary online [accessed July 2017]). The price of sorafenib is 3,576.56 GBP per 112×200 mg pack (excluding VAT; British national formulary online [accessed July 2017]). The companies have commercial agreements. This makes lenvatinib and sorafenib available to the NHS with a discount. The size of the discount is commercial in confidence. It is the companies’ responsibility to let relevant NHS organisations know details of the discount.