Draft NICE guidance denies RCC drugs

The UK's National Institute for Health and Clinical Excellence (NICE) has issued preliminary recommendations for the treatment of renal cell carcinoma (RCC), concluding that Roche/Genentech's Avastin (bevacizumab), Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib), Pfizer's Sutent (sunitinib) and Wyeth Pharmaceuticals' Torisel (temsirolimus) are not recommended as treatment options for advanced and/or metastatic disease. Although the drugs were shown to be clinically effective and extend life for RCC patients, they were deemed to not be a cost-effective use of NHS resources. NICE is expected to issue final guidance in January 2009.

Following the decision, Cancer Research UK (CRUK) has called for NICE to alter the way that it appraises the value of drugs for rare diseases, such as metastatic RCC, where clinical benefit is proven but evidence is limited due to the small number of available patients. Professor Peter Johnson, CRUK's chief clinician, stated: "We are disappointed at NICE's view that although these drugs are clinically effective, their high price means that they are not considered to be value for money for the NHS. These drugs have shown a small but definite improvement in an illness where there are few alternative treatments. If this decision stands it will be very frustrating for cancer patients and their clinicians."

The charity put forward that possible solutions include looking at the way that pharmaceutical companies are charging the NHS for drugs, and whether appropriate allowances are being made by NICE to compensate for the lack of large-scale trials in these areas. However, it turns out that proposals were submitted by two of the manufacturers relating to drug acquisition costs. But these were not considered by the Department of Health as they had not been agreed before the appraisal.

The preliminary guidance raises questions as to how NICE evaluates cancer drugs, particularly for cancers that only affect a relatively small number of people. The gold-standard method of testing whether a treatment works and is safe is through the use of clinical trials. The larger the number of patients enrolled in a study, and the longer it lasts, the more sure researchers can be about its results. This works for diseases that affect large numbers of people, such as breast and lung cancer, but only around 2,000 people every year are diagnosed with metastatic RCC. Further, only one in ten people diagnosed with this stage of the disease is alive five years later. This means that for relatively rare diseases like this, it can take a long time to conduct large enough studies to gather the evidence needed to gain approval from regulatory agencies.

Even if these studies do demonstrate benefit, as those for the four drugs did, there is still the cost-effectiveness hurdle to overcome. When NICE analysed the data from the trials with its models, it found that the drugs were expensive (around £20,000 to £35,000 per patient per year) compared to the benefit they brought patients. However, concerns have also been raised about these models, which are designed to examine giving drugs to large numbers of people. Are they equally valid for looking at relatively uncommon diseases, such as metastatic RCC? Hopefully NICE will be able to answer these questions when its final guidance is published.

Matthew Dennis - Editor, Cancer Drug News