The National Institute for Health and Clinical Excellence (NICE) has issued new draft guidance in which it does not recommend Pfizer's tyrosine kinase inhibitor ((TKI) Xalkori (crizotinib) for use in previously treated anaplastic-lymphoma-kinase-(ALK) positive advanced non-small-cell lung cancer (NSCLC), but has opened a public consultation on this preliminary decision.

NICE chief executive Sir Andrew Dillon points out that the Institute has already recommended a number of treatments for the various stages of NSCLC, and that the independent committee which considered the evidence for Xalkori had concluded that the drug is a clinically-effective treatment for ALK-positive NSCLC. However, even if NICE's supplementary advice to the committee for life-extending treatments had been applied, it could not be considered a cost-effective use of NHS resources, he says.

While NICE appraisal committees normally recommend treatments costing around £20,000-$30,000 per quality-adjusted life year (QALY) or less, a higher cost per QALY may be accepted if the drug meets the criteria to be considered under this supplementary advice. There is no set threshold cost per QALY for drugs that meet the end-of-life criteria but, since the supplementary advice was introduced, the highest cost per QALY of a recommended drug has been around £50,000.

However the committee concluded that the most plausible cost per QALY for Xalkori when compared with docetaxel would lie somewhere between £63,000 and £181,000, and that, when compared with best supportive care, it would be between £51,700 and £80,000.

Pfizer has expressed disappointment at NICE's preliminary rejection of Xalkori in this indication. The drug has a conditional licence for use in patients with previously-treated ALK-positive advanced NSCLC, it says, pointing out that this is the only therapy approved specifically for this subset of NSCLC cases and that it signals one of the most recent advances in personalised therapy in lung cancer.

"In an aggressive disease like advanced lung cancer, where, for the majority of patients, survival is exceptionally poor and where not all patients can expect to gain much benefit with existing therapies, there is an urgent need for new medicines like crizotinib which target the specific drivers of a patient's tumour," said Dr Michael Peake, clinical lead at the National Cancer Intelligence Network and National Cancer Lead at NHS Cancer Improvement.

"Clinicians recognise that the future of cancer treatment lies in these types of targeted medicines. If this preliminary guidance is upheld, it potentially signals a setback to the advancement of cancer medicine in the UK," he warned.

Dr David Montgomery, medical director at Pfizer Oncology UK, pointed out that personalised medicines are developed specifically for selected subgroups of patients who are most likely to benefit, sparing those in whom they will have no effect.

"We believe this approach is better for patients and offers better value for the NHS, a concept in keeping with NICE's purpose," he said, adding: "we are committed to working through the NICE consultation process to address the uncertainties within this preliminary recommendation."

NICE's Appraisal Consultation Document (ACD) shows that the Institute accepts that Xalkori offered patients a "noteworthy" improvement in progression-free survival and that the number of patients responding to treatment was “very high" for a second-line therapy in this difficult-to-treat cancer, says Pfizer. The firm also points to NICE's acknowledgement that the drug was likely to extend patients' lives, although it was uncertain by how long, and that NICE's conclusion that Xalkori was not cost-effective was due, in part, to uncertainty in estimating the magnitude of overall survival benefit attributed to the drug.

"Like many trials for oncology medicines, the crizotinib trial was designed to give patients in the chemotherapy arm the opportunity to receive crizotinib once their cancer had progressed. This factor makes it difficult to compare the differences in overall survival between the two arms of the trial, because both groups of patients will have received crizotinib. Therefore, obtaining the proof NICE requires for these medicines is very difficult," says Pfizer.

"There remains a great need for either a new approach to account for this ethically important factor of clinical trial design or for changes to the technology assessment process to take this into account," the firm adds.