NICE Issues Technology Appraisal Guidance for Brigatinib

It is recommended in patients with ALK-positive advanced NSCLC who have already had crizotinib

On 20 March 2019, NICE issued Technology appraisal guidance [TA571] with evidence-based recommendations on brigatinib (Alunbrig, Takeda) for treating anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) in adults who have already had crizotinib.

Brigatinib is recommended, within its marketing authorisation, for treating ALK-positive advanced NSCLC in adults who have already had crizotinib. It is recommended only if the company provides it according to the commercial arrangement.

The recommended starting dosage of brigatinib is 90 mg once daily for the first 7 days, then 180 mg once daily. Treatment should continue as long as there is clinical benefit.

If brigatinib treatment is interrupted for 14 days or longer for reasons other than adverse reactions, treatment should be resumed at 90 mg once daily for 7 days before increasing to the previously tolerated dose.

If a dose is missed or vomiting occurs after taking a dose, an additional dose should not be administered, and the next dose should be taken at the scheduled time.

The proposed list price for brigatinib is 4,900 GBP for 28×180 mg tablets (the recommended dose), 4,900 GBP for a starter pack (7×90 mg plus 21×180 mg tablets), 3,675 GBP for 28×90 mg tablets, 1,225 GBP for 28×30 mg tablets (company submission).

The company has a commercial arrangement. This makes brigatinib available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know details of the discount.

Why the appraisal committee made these recommendations?

Patients with ALK-positive advanced NSCLC that have been treated with crizotinib are currently offered ceritinib as their next treatment.

Clinical evidence based on indirect comparisons of trials suggests that patients having brigatinib live longer than those having ceritinib, and that they live longer before their condition worsens. Brigatinib may be more effective for brain metastases and better tolerated than existing treatments.

The cost-effectiveness estimates are uncertain, particularly because of whether brigatinib's treatment benefit continues after stopping treatment. The most plausible estimates for brigatinib compared with ceritinib are around the higher end of what NICE normally considers acceptable for an end-of-life treatment. But the population eligible for brigatinib is small and will decrease because crizotinib is no longer considered first-line treatment for ALK-positive NSCLC. Future treatments will be limited for those who have crizotinib. Taking these exceptional circumstances into account, brigatinib is recommended for ALK-positive advanced NSCLC in adults who have had crizotinib.

Next review is foreseen for March 2022.