Sanofi’s prostate cancer drug Jevtana (cabazitaxel) has not been recommended by NICE in draft guidance in combination with prednisone or prednisolone as a second line treatment.

NICE’s Appraisal Committee raised concerns about the medication’s cost effectiveness, its associated adverse effects and evidence supplied by the manufacturer.

Sir Andrew Dillon, NICE Chief Executive, says that the Committee was “particularly concerned” about the uncertainty on patients’ renal and cardiac systems.

A number of factors are taken into consideration by NICE’s Appraisal Committees when assessing the cost effectiveness of a treatment. These include the medication’s clinical effectiveness, its side effects, the benefits it brings to patients and the financial cost.

This formula then enables them to determine the cost of using the drug to provide a year of the best quality of life available or quality adjusted life year (QALY). NICE says they usually recommend treatments that cost around £30,000 per QALY or less, however the cost of Jevtana was far greater than this figure.

“The manufacturer of cabazitaxel provided one study on the effectiveness of the drug; in this study cabazitaxel was shown to extend life by approximately 10 weeks,” said Sir Andrew. “Although cabazitaxel has been shown to be effective, it is also associated with a number of adverse events.”

He added that the Appraisal Committee was also concerned about the “validity” of the health related information supplied by Sanofi after it provided one study which demonstrated a median overall survival gain of 2.4 months and an mean overall survival gain of 4.2 in its model.

“The Committee also felt that the treatment did not meet the criteria to be considered under NICE’s special arrangements for end of life, as based on the current data the length of the life extension could not be considered robustly proven to be at least three months,” added the Chief Executive.

“Once all these factors had been taken into account it was estimated that the cost per QALY would be more than £89,000. Therefore the committee concluded that cabazitaxel would not be a cost effective use of limited NHS resources.”

If a drug does meet the criteria to be considered under the Institute’s supplementary advice for end of life treatments, a higher cost per QALY may be accepted by NICE. There is currently no set threshold cost per QALY that meets this criterion, but since the supplementary advice was introduced, the only drug recommended under this method has been Sunitinib for renal cell carcinoma at a cost of £50,000.

NICE said that Javtana did not meet this criterion because the Committee did not consider the length of the life extension to be “sufficiently robust”.

Novartis has received approval from the European Commission for the use of Afinitor (everolimus) tablets to treat patients with advanced pancreatic neuroendocrine tumours (NET).

The decision was based on Phase III data which indicated the tablets more than doubled the time without tumour growth.

Hervé Hoppenot, President, Novartis Oncology, says the approval means thousands of patients “will have a new targeted approach” for the aggressive cancer.

The decision applies in all 27 European Union states, plus Iceland and Norway. Novartis are also currently seeking additional regulatory submissions across the rest of the world.

The RADIANT-3 Phase III trial was the largest clinical trial to date in advanced pancreatic NET. Results found that Afinitor reduced the risk of cancer progression by 65% when compared with placebo in patients with advanced stages of the disease.

An improvement in progression-free survival was also found in all patient subgroups, including those who had not received prior chemotherapy.

Afinitor is currently approved in the EU for the treatments of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy.

It is also approved in Europe for the non-oncology patient population under the trade name Certican for the prevention of organ rejection in heart and kidney transplant recipients.

NICE has recommended Votrient (pazopanib), a targeted oral treatment that has been proven to slow down the progression of advanced kidney cancer.

The Final Appraisal Determination (FAD) recommends Votrient as a first-line treatment option for people with advanced renal cell carcinoma (RCC) who have not previously received cytokine therapy and who are of Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

GSK and NICE have agreed a patient access scheme that includes a discount on the price of the drug and a possible partial rebate to the NHS in the future, to be paid if the ongoing head-to-head study is unable to confirm the value of Votrient versus the current standard of care.

Votrient is only the second targeted treatment option to be recommended by NICE for this patient group.

Simon Jose, General Manager, GlaxoSmithKline (GSK) UK, commented: “It is often difficult to demonstrate the full value of innovative cancer medicines initially, as the evidence driving that value typically evolves over time as further studies are completed. We recognise this challenge and that is why we have offered an innovative potential future value rebate scheme.

“This is great news for patients and physicians who can have rapid and equitable access to this treatment, good for the NHS as it delivers value for money and also allows GSK to achieve a fair return for its innovation.”

NICE has failed to recommend Novartis’ Afinitor (everolimus) for the second-line treatment of advanced renal cell carcinoma (RCC).

Draft guidance concluded that Afinitor does not provide enough benefits to justify its high cost, despite Novartis submitting an amended Patient Access Scheme (PAS).

Sir Andrew Dillon, NICE Chief Executive, said there is ‘too much uncertainty’ around the drug’s cost effectiveness.

A PAS which offered a 5% discount was initially agreed between Novartis and the DH, but a further offer was then devised – and agreed again – following the publication of the first Final Appraisal Determination (FAD).

As a result, the consultation on the original FAD was suspended and a new appraisal began.

“NICE asked the independent Appraisal Committee to consider the newly amended patient access scheme and a further cost effectiveness analysis that NICE asked the manufacturer to provide,” said Sir Andrew. “However, the committee felt that there was still too much uncertainty around how cost effective everolimus is to enable the committee to recommend the drug.”

Evidence suggests that Afinitor increased survival by more than three months compared with best supportive care. Sir Andrew Dillon understood that patients may be unhappy about the decision, but NICE could not provide a recommendation at this difficult financial time.

“We know that patients with renal cancer want to try all the treatment options and are disappointed not to be able to recommend everolimus as a second line treatment option,” he added.

“However, we have to ensure that the money available to the NHS, for treating cancer and other conditions is used to best effect, particularly when NHS funds, like the rest of the public sector, is under considerable financial pressure.”

The number of people diagnosed with advanced RCC each year is less than 4000. But those eligible for Afinitor, who have received first-line treatment (Sutent) sunitinib and are still fit enough to receive a second-line treatment, would be lower.