Draft guidance from NICE does not recommend Avastin (bevacizumab) for treatment of recurrent advanced ovarian cancer.

NICE’s appraisal committee determined that the Roche drug, when used in combination with the chemotherapy drugs gemcitabine and carboplatin, did not represent good value for the NHS.

The main reason for the decision was that clinical data were unavailable for a third of clinical trial participants, for reasons unknown to NICE.

Recurrent advanced ovarian cancer, when the cancer has returned following initial treatment and has spread beyond the ovaries, is terminal. However, NICE did not accept that Avastin qualified as an end of life treatment.

Roche’s submission highlighted the fact that Avastin together with chemotherapy offers a median progression-free survival benefit of four months more than chemotherapy alone.

However, NICE stated that “the data from around 30 of the patients had been censored” and the impact of that on progression-free survival rates was “unclear”.

The committee further noted that Roche’s estimated ICER of £149,050 per QALY gained “was likely to be optimistic”.

In addition, it said, there was insufficient evidence of overall survival benefit, and there was no patient access scheme. The latter has become a key deal-breaker for NICE in recent years.

Ovarian cancer affects around 7,000 new patients in the UK each year, and Roche estimates that over 2,000 women would be eligible for treatment with Avastin if it were approved in this indication.

Avastin has received several NICE rejections in recent years, as it offers some progression-free survival benefit but is costly. Many UK patients currently receive it via the Cancer Drugs Fund, which is soon to be discontinued.

NHS England has announced a new national system for the Cancer Drugs Fund designed to end regional variation in ‘fast-track’ access to cancer drugs.

However, according to the charity Macmillan Cancer Support, the new system has halved the number of indications for which drugs are covered by the fund.

The single national list of drugs approved for ‘fast-track’ funding contains 28 drugs to treat 64 cancer indications, compared to the 129 previously covered by the ten SHAs through the Fund.

The Cancer Drugs Fund, which was established in 2010 and will end in March 2014, provides £200m per year for access to drugs not approved as cost-effective by NICE but requested by doctors for individual patients.

NHS England (formerly the NHS Commissioning Board) took over responsibility for management of the Cancer Drugs Fund from 1 April, ending the regional administration that had seen variations in access to cancer drugs.

Sean Duffy, NHS England’s National Clinical Director for Cancer, said: “Having one consistent method for consideration of overall clinical benefit and funding means that all applications will be assessed by the same criteria. Regional variation of the past is clearly not acceptable for patients.”

Any patient who is already receiving funding for a cancer drug, or has been told they will receive funding as part of an agreed treatment plan, will continue to receive that treatment where clinically appropriate.

The single drugs fund list was developed by the National Cancer Action Team together with the regional clinical leads for the ten former SHAs. A national Clinical Reference Group for Chemotherapy, appointed by NHS England, has approved the proposed list.

However, Mike Hobday, Head of Policy and Research at Macmillan Cancer Support, commented: “It is worrying that the reduced list of cancer drugs that can be funded will restrict access to drugs which were previously routinely available. For rarer cancers, this will be particularly acute.”

NICE has again failed to recommend Roche’s cancer drug Avastin (bevacizumab) – this time in new draft guidance for the treatment of metastatic ovarian cancer.

An independent Appraisal Committee decided that Avastin is not a cost-effective treatment option after a consultation period, following initial draft guidance issued in December 2012.

Roche said it was “disappointed” by NICE’s decision and claims that Avastin is the only drug proven to improve outcomes in women with ovarian cancer in the last 15 years.

Avastin recently failed to gain a recommendation as a treatment option for advanced ovarian cancer in separate guidance with NICE again citing cost reasons.

The most recent appraisal assessed whether Avastin, when used in combination with the chemotherapy treatments paclitaxel and carboplatin, would be a cost-effective option for the NHS. Avastin’s licensed dose is 15mg per kilogram of body weight – although many doctors use lower dosages when treating patients.

NICE’s assessment considered the treatment according to its marketing authorisation and not in line with current practice, which saw its cost-effectiveness analysis fall outside the range considered for NHS use.

Roche, who did not submit a patient access scheme to lower the cost of the drug, said that women will now have to rely on the Cancer Drugs Fund (CDF) to access the treatment.

But it raised questions around the “considerable uncertainly” on how medicines currently funded by the CDF will be available to patients when the scheme ends in March 2014. Roche has called for “a clear transition plan” for such medicines to reassure patients currently using these treatments.

The updated draft guidance is now subject to a two-week appeal period.

The Scottish Medicines Consortium (SMC) has declined to recommend the use of Avastin (bevacizumab) for women with recurrent ovarian cancer.

According to SMC, Roche’s drug confers up to four months’ additional progression-free survival when combined with standard chemotherapy, but the benefit does not justify the high cost.

NICE provisionally made the same decision in December – but in England, the Cancer Drugs Fund (soon to be cancelled) makes the drug available for this indication in selected patients.

SMC, like NICE, has already decided not to recommend Avastin for treatment of newly-diagnosed advanced ovarian cancer.

Avastin is given in combination with standard chemotherapy, as a three-weekly infusion, to patients with recurrent ovarian cancer after first-line treatment. It works by blocking the growth of new blood vessels to the tumour cells.

SMC noted that patients in a clinical trial showed an extra four months’ survival without cancer progression when Avastin was added to their chemotherapy. However, it said, there was “uncertainty” regarding the effect on overall survival.

In addition, “the cost in relation to the health benefit was significantly above the threshold normally accepted by SMC”.

Avastin has a history of being licensed for cancer treatment, but not recommended as cost-effective.

Medical writer Ben Goldacre has argued that the profusion of indications for which the drug has been proposed is a result of recurrent “sub-group analysis”, while so far Roche has only published the results of 10 out of 24 phase III studies.

However, the question of what price can be paid for months of progression-free survival is also crucial at a time of increasing pressures on health service budgets.

Professor Charlie Gourley, Honorary Consultant in Medical Oncology, University of Edinburgh, commented: “It is extremely disappointing that oncologists in Scotland who treat women with recurrent ovarian cancer do not have access to Avastin. The negative SMC decision and the lack of a Cancer Drugs Fund in Scotland will prevent patients benefitting from an extra four months without the signs and symptoms of their disease.”

The UK has one of the highest rates of incidence of ovarian cancer in Europe – as well as one of the highest mortality rates, with the disease killing over 4,000 women each year.

The Government will use £15m from the Cancer Drugs Fund for a new nationwide radiotherapy programme aimed at providing nearly 8,000 patients a year with life-saving advanced therapy.

The Cancer Radiotherapy Innovation Fund, which will commence next April, will increase the use of Intensity Modulated Radiotherapy (IMRT) across the NHS.

IMRT targets more precise doses of radiation at tumours whilst minimising the impact on surrounding health tissue thus reducing side effects.

Health Secretary Jeremy Hunt said radiotherapy is one of the most “clinically and cost-effective treatments for cancer” available to the NHS.

The investment will be funded from any under spend arising from the Drug’s Fund in 2012-13. If there is no under spend, the money will be taken from other budgets, the DH confirmed.

Radiotherapy experts, Cancer Research UK and other relevant professional bodies will work together to ensure designated centres adopt the new technique and provide innovative therapy that is clinically appropriate, safe and cost effective.

Prime Minister David Cameron said the new fund would ensure patients get the “drug and treatments they need”.

“We already have a guarantee for drugs – that if they’re safe, cost-effective and doctors say you need them, you will get them,” he said. “From April 2013, for the first time ever, we’re extending that guarantee to radiotherapy too. This is going to help thousands of people at one of the hardest times of their lives.”

Value-based pricing (VBP) is a more fair and balanced way of supplying life-saving drugs for patients than the Government’s Cancer Drugs Fund, a new study shows.

Research by the University of Bangor found that out of more than 4,000 people across Britain 64% agreed that the NHS should not pay more for cancer drugs compared to medicines for other threatening conditions.

Professor Dyfrig Hughes, study author, said “singling out cancer seems to be unfair, but is something which will hopefully be addressed in the value-based pricing system, which has public support.”

The Cancer Drugs Fund was introduced two years ago for the NHS to treat patients with oncology treatments not currently recommended by NICE. It supplies £200m a year until 2013 to pay for drugs.

VBP is the Government’s alternative to the existing 2009 PPRS pricing scheme – set to expire in 2013. It will allow government to set prices for new medicines as they enter the UK market – and set new definitions of value.

Although it has gained support from the general public, the ABPI has raised a number of concerns about the new system and is in negotiations with the Government to create an amended version.

“The funding of high cost cancer treatments is clearly an emotive issue, and it is for politicians to determine the parameters by which the NHS pays for them, however, there are equally distressing conditions affecting patients who are equally deserving, but they have no access to ring-fenced budgets,” said Professor Hughes.

The Rarer Cancers Foundation (RCF) has called for action to ensure that when the Cancer Drugs Fund ends, access to drugs for rare cancers continues.

Over 16,000 NHS patients per year may lose access to life-extending drugs when the fund ceases in March, the charity warns.

It suggests that a “transitional” continuation of the Cancer Drugs Fund (CDF) may be needed while steps are taken to ensure that new pricing and prescribing arrangements maintain these treatments.

The CDF provides £200m per year for trusts to purchase cancer drugs that do not have NICE approval.

According to the RCF’s new report on the fund’s impact, it has enabled over 3,600 patients with rarer cancers to access treatments in the last year.

The report points out that the fund has enabled NICE to increase its cancer drug rejection rate from 40% to 60% by making cost a higher priority.

It recommends that NHS authorities examine variations in access to cancer drugs according to location and age, leading to “an urgent review” by the NHS CB of “population cohort policies for funding cancer treatments”.

The RCF also calls for “national protocols” for off-label cancer treatments to be established, allowing their efficacy and safety to be assessed.

Looking forward, it says the DH “should clarify as a matter of urgency how it intends to ensure access to treatments currently reimbursed through the Cancer Drugs Fund in 2014 and beyond.”

The review proposes two measures:

• a mechanism to include these treatments in the new value-based pricing framework, with the CDF being extended as a “transitional” system if necessary

• a national system for off-label prescribing of rare cancer drugs that cannot be covered by VBP.

Roche has questioned the methods used by NICE in its appraisal of Avastin (bevacizumab) after it was not recommended as a first line treatment for advanced breast cancer in draft guidance.

Avastin, in combination with Xeloda, was being appraised in patients whom treatment with chemotherapy options, including taxanes or anthracyclines, is not considered appropriate.

However, Roche said NICE had a “lack of belief in a biologically plausible explanation for why Avastin works so well” which resulted in the failure to recommend the treatment.

The Swiss-based company claim the Institute ignored the progression free survival (PFS) and overall survival benefits of the drug demonstrated in clinical trials. Instead Roche said NICE chose to review data in the context of the entire population of women with metastatic breast cancer.

NICE admits evidence supplied by Roche did suggest Avastin “could delay cancer from progressing” longer than Xeloda alone, but said there was no evidence which showed it led to “an improvement in overall survival”.

Sir Andrew Dillon added there was no information available on whether Avastin improves a patient’s quality of life. “Taking these uncertainties into account as well as the high cost of the drug, the committee concluded that bevacizumab was not a cost-effective use of NHS resources,” he said.

Patients with metastatic breast cancer can still apply for access of Avastin through the Cancer Drugs Fund.

Final guidance is now expected in August 2012.

The NHS maintained or improved performance in 2011/12 against a range of indicators outlined in the NHS Operating Framework, the Secretary of State’s Annual Report says.

The report noted that the “NHS has performed well” over the last twelve months whilst meeting the first stage of its efficiency savings target.

Health Secretary Andrew Lansley said NHS staff across England have “maintained or improved quality while making significant cost savings and preparing for the transition to the new system”.

The annual report has been published a year earlier than required by law. The move was made by the Health Secretary to allow Parliament and the public to see the “direction the NHS is heading”, the Department of Health said.

It found that 212 CCGs are now on their way to being authorised by January next year. Also, as of April this year, there were 144 Foundation Trusts (FT), with 104 trusts remaining in the FT pipeline. Of these, only 18 trusts were not making progress towards gaining FT status and were in discussions with the DH to “develop recovery plans and progress towards sustainable, high-quality services”.

In future, the report will analyse the performance of the NHS against the three outcomes frameworks – NHS, public health and adult social care. As these are still being developed, it focused on “key achievements” during 2011/12.

It found that the QIPP agenda had generated savings of £5.8 billion; more than 12,500 patients had accessed the Cancer Drugs Fund; maximum waiting times for diagnosed and suspected cancer patients were met; and more people with diabetes are now being offered diabetic retinopathy screening than ever before.

Despite the structural reforms to the NHS, cost-cutting measures and the rationing of services, the report included data from a recent MORI poll which found that nearly three-quarters (73%) agreed that England had one of the best national health services – the highest level ever recorded.

Andrew Lansley said that performance data has “undoubtedly been positive”, but there were a number of “significant challenges” facing the health service. “Compared to other countries we continue to lag on performance on some key outcomes including life expectancy for women, cancer survival, and conditions related to obesity,” he said.

To meet “continued pressure” on finances, Lansley said there will need to be “sustained efforts to ensure that every penny of public money is spent as effectively as possible, delivering the best possible outcomes for patients.”

Future annual reports are expected to be published in October to allow Arm’s Length Bodies time to publish their own reports and accounts for the financial year.

The Department of Health may be leaving the details of its value-based pricing policy for NHS drugs “too late” for industry, Roche has warned.

The Cancer Drugs Fund will end just as VBP is introduced in 2014 – potentially leaving doctors unable to prescribe certain cancer drugs if companies have not had time to make their case.

Gavin Lewis, Roche’s UK Director of Health Economics and Strategic Pricing, said major cancer drugs such as Avastin, Erbitux and MabThera were in danger of becoming unavailable.

Speaking to the National Cancer Intelligence Network, Lewis said that companies whose drugs were only available through the CDF were waiting to be told how to gain NHS access under VBP.

“The reality is there is still silence,” he said. “And if you really want to have continuity of access to these cancer drugs and still have VBP at the end of 2013, then you could start saying it’s too late to start that process.”

Roche’s Avastin, which lacks NICE recommendation, is a leading example of a cancer drug whose future is in doubt as the pricing system changes.

NICE has proved hard to convince that high-cost cancer drugs are cost-effective, but the CDF commits £200m per year to buy them for NHS patients.

The ABPI anticipates that drug pricing negotiations between industry and the DH will begin in September.