The National Institute for Health and Clinical Excellence (NICE) announced its decision not to recommend Afinitor (everolimus) for advanced kidney cancer patients who have relapsed following initial therapy. The conclusion of the Final Appraisal Determination (FAD) comes despite Novartis Oncology providing a discount-based patient access scheme and NICE acknowledging everolimus as the only licensed treatment proven to be clinically effective for advanced kidney cancer patients who have failed on the only NICE approved first-line therapy.2,5 In response to this disappointing decision, Novartis Oncology has announced it will file an appeal.

"This decision means that patients are not getting access to an effective cancer treatment that is widely available in other EU countries", commented Dr Thomas Powles, Consultant Medical Oncologist at Barts and the London NHS Trust. "Everolimus works in patients with treatment resistant kidney cancer and it doubles the amount of time they can live without their disease progressing. NICE's rejection is based on a lack of cost-effectiveness rather than clinical effectiveness. Luckily the new Government's Interim Cancer Drug Fund already allows some patients to gain access to everolimus on the basis of this clinical activity, therefore although NICE's decision is final, it does not mean that patients in the UK can't potentially have access to this drug."

Every year over 8,000 new cases of kidney cancer are diagnosed in the UK; almost half (3,848) of which will result in death.3,4 40 per cent of patients will be diagnosed in the advanced stages when prognosis is extremely poor and treatment options are limited.6

The European Medicines Agency (EMA) approved everolimus for the treatment of patients with the commonest form of advanced kidney cancer known as renal cell carcinoma (RCC), after failure of treatments which prevent the growth of the tumour's blood vessels on 3rd August 2009.7 Everolimus is reimbursed in other EU countries including Belgium, Denmark, Germany, Finland, France, Greece, Ireland, Luxemburg, the Netherlands, Slovakia, Spain and Switzerland. Prior to this, there was no licensed treatment option for advanced kidney cancer patients with RCC whose cancer progressed while on or after treatment with the only NICE approved first-line therapy. Expert consensus opinion, published in a review journal, recommends everolimus as a treatment option for this form of advanced kidney cancer therapy after progression on targeted therapy.8

Panos Alexakos, Oncology General Manager for Novartis UK and Ireland, commented, "It appears that the NICE process does not take into account the full value of oncology medicines. Not only is there robust data to demonstrate the clinical and cost-effectiveness of everolimus in an area of unmet clinical need, we also strongly believe that the treatment is within the cost/QALY range considered acceptable under the 'end of life' criteria."

The FAD provides a recommendation on whether this medicine should be funded by the NHS. The FAD states that although NICE acknowledges the clinical effectiveness of everolimus and recognises that patients have no other effective licensed treatment option, the medicine is not considered to be "cost effective" and would not represent an appropriate use of NHS funds.2

According to the recent "Extent and causes of international variations in drug usage" report by the Department of Health, the UK ranks relatively low in terms of usage for cancer drugs launched within the last five years.9

Notes

NICE timings

The Final Appraisal Guidance document for everolimus is expected to be published on 26 November 2010.

About 'end of life' criteria

The NICE 'end of life' criteria are as follows:

- The treatment is indicated for patients with a short life expectancy, normally less than 24 months

- There is sufficient evidence to indicate that the treatment offers an extension to life, normally of at least an additional 3 months, compared to current NHS treatment

- The treatment is licensed or otherwise indicated, for small patient populations10

The NICE Committee was satisfied that everolimus met the criteria for being a life-extending, end-of-life treatment, and that the evidence presented for this consideration was sufficiently robust.2

About kidney cancer

Kidney cancer accounts for approximately 3% of all new cases of cancer diagnosed in men and just over 2% of all cancers in women in the UK.3 The incidence of kidney cancer in the UK is increasing, due in part to obesity and smoking.11

In kidney cancer, cancer cells develop in the lining of the kidney's tubes and grow into a tumour. If left untreated, the tumour can spread to neighbouring lymph nodes and eventually to other organs.

About everolimus

In the UK, everolimus is indicated for patients with a form of advanced kidney cancer known as renal cell carcinoma, whose disease progressed on or after treatment with VEGF-targeted therapy.8

In cancer cells, everolimus continuously targets the mammalian target of rapamycin (mTOR), a protein that acts as a central regulator of tumour cell division, blood vessel growth and cell metabolism.12

The European Medicines Agency (EMA) approved everolimus for the treatment of renal cell carcinoma after failure of treatments which prevent the growth of the tumour's blood vessels on 3rd August 2009.7 Prior to this, there were no licensed treatment options for advanced kidney cancer patients whose cancer progressed while on or after treatment with these targeted VEGF therapies.5 UK expert consensus opinion, published in a review journal in May 2009, recommends everolimus as a treatment option for this form of advanced kidney cancer therapy after progression on targeted therapy.8

Data that led to the European approval shows that everolimus, when compared with placebo, more than doubled the median time without tumour growth or death in patients with advanced kidney cancer whose disease progressed following prior VEGF-targeted therapy (4.9 vs. 1.9 months).13,5 The data showed the reduction of the risk of disease progression or death to be 67% based on the primary endpoint of progression-free survival (PFS) (hazard ratio=0.33 with 95% confidence interval 0.25 to 0.43; P