The National Institute for Health and Care Excellence (NICE) has issued final draft guidance which does not recommend Pfizer's Xalkori (crizotinib) for previously-treated anaplastic-lymphoma-kinase-positive advanced non-small-cell lung cancer (NSCLC). 

Xalkori is a tyrosine kinase inhibitor, which works by blocking enzymes which can stimulate cancers to grow. The drug blocks a specific enzyme, anaplastic lymphoma kinase (ALK), which is present in some NSCLCs.

Commenting on the draft guidance, NICE chief executive Sir Andrew Dillon said that during the consultation on the draft, Pfizer had submitted further information for NICE's independent appraisal committee to consider. This included a patient access scheme (PAS) which involves providing the drug to the NHS at a discounted price, the level of which is commercial in confidence. A revised cost-effectiveness analysis was also submitted to the panel.

Treatment with Xalkori resulted in a median gain of 5.1 months in progression-free survival compared with docetaxel, although the exact magnitude of the overall survival gain was uncertain because of the immaturity of the trial data and the impact of crossover in the trial, says NICE.

The committee had concluded that the cost per quality-adjusted life year (QALY) on which to base a decision for Xalkori compared with docetaxel would be more than £100,000 per QALY gained, and for Xalkori compared with best supportive care would be over £50,000 per QALY gained.

The drug's acquisition cost is £4,689 for one pack of 60x200mg (or 250mg) capsules, a 30-day supply. Assuming treatment until disease progression, the cost of a course of treatment would be £37,512-£46,890 and, assuming treatment after disease progression, cost of a course of treatment would be £51,579.

Sir Andrew pointed out that NICE has already recommended a number of treatments for the various stages of NSCLC. He added that while the independent committee which considered the evidence found Xalkori to be a clinically-effective treatment for ALK-positive NSCLC, it could not - even when the manufacturer's discount had been applied - be considered a cost-effective use of NHS resources.

The draft guidance is now with consultees, who have the opportunity to appeal against it. 

Pfizer has expressed its "concern and disappointment" at the decision, and about the impact that it will have on eligible patients with previously-treated NSCLC whose tumours have been identified as ALK-positive.

"As a personalised medicine, crizotinib allows targeted treatment of a specific group of patients who are most likely to benefit. In reality, the UK's limited and slow-paced adoption of innovative medicines such as crizotinib poses a real threat to both the government's goal to have UK cancer outcomes among the highest in Europe and its vision to make the UK a world leader in life sciences," says the firm.

Following NICE's decision, the only other route for patients with previously-treated, ALK-positive advanced NSCLC to access crizotinib is through the National Cancer Drugs Fund (CDF). However, this is only available to patients in England, treatments are not guaranteed to stay on it and the future of its existence remains unknown, Pfizer adds.

- Xalkori was launched in the UK at the end of 2012. Around 41,500 new cases of lung cancer are diagnosed in the UK every year, around 85% of which are classed as NSCLC, and some 3%-5% of NSCLC tumours are estimated to be ALK-positive.