Draft guidance from NICE does not recommend Avastin (bevacizumab) for treatment of recurrent advanced ovarian cancer.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

Scottish author Iain Banks has only months to live, following a diagnosis of late-stage cancer.

Banks, author of such ground-breaking contemporary novels as The Crow Road and Complicity, has said that his forthcoming novel The Quarry will be his last.

Writing on his personal website, Banks said he had been diagnosed with cancer of the gall bladder that had spread too far to be operable.

The option of chemotherapy was still being considered, he said, with “pros and cons” to be balanced.

“From my GP onwards, the professionalism of the medics involved – and the speed with which the resources of the NHS in Scotland have been deployed – has been exemplary, and the standard of care deeply impressive,” Banks commented. “We’re all just sorry the outcome hasn’t been more cheerful.”

From The Wasp Factory (1984) to Stonemouth (2012), Banks’ novels have dealt with such themes as crime, alienation, mortality and injustice. He has been acclaimed as one of the great humanist writers of his generation.

As Iain M. Banks, he has also written a series of science fiction novels exploring the practical, political and ethical challenges of the future.

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.

NHS chemotherapy services are being stretched to the limit by the combination of increased demand and reduced funding, a new report from Roche warns.

The drug company has published The Cancer Capacity Challenge, which argues that new systems to deliver chemotherapy more rapidly and cheaply are needed.

Over 70% of oncology specialist nurses, responding to questions from their colleagues, said lack of capacity to deliver the service was harming care.

The report says that improvements in diagnosis and treatment have increased the life expectancy of patients with cancer – but this in turn has increased the level of demand for services.

According to oncology specialist nurses surveying the views of their colleagues:

• 71% believe patient care is suffering from lack of NHS capacity in chemotherapy

• 76% believe waiting times for chemotherapy are set to increase

• 67% said their day units are fully stretched or over-full.

The incidence of cancer in the UK has increased by 20% in men and 40% in women over the last 30 years, due primarily to the ageing population.

The CCC report recommends that the capacity of chemotherapy services could be increased by treating more patients at home or in primary care.

To facilitate this, Roche argued, there is a need for chemotherapy drugs that can be administered more quickly and easily in a range of settings. The report suggests that Roche may be planning new products in this important area.

Kate Denby, Haematology Advanced Nurse Practitioner, Royal Exeter and Devon NHS Foundation Trust, said: “The steps involved in each patient visit can take as long as seven hours. Patients usually prefer shorter visits to hospital for their chemotherapy treatment, so it’s essential that we are able to find solutions that help improve the patient experience.”

An established blood cancer drug is now available in a subcutaneous form, cutting the administration time from two hours to five minutes.

The subcutaneous (SC) form of Roche’s MabThera (rituximab), used to treat non-Hodgkin lymphoma (NHL), could improve patient experience while freeing up time in chemotherapy suites.

MabThera SC uses a new biological technology from Halozyme that locally and reversibly breaks down sub-skin tissues.

The SABRINA phase III trial compared the effects of MabThera SC and MabThera IV in patients with previously untreated follicular lymphoma.

It proved the non-inferiority of MabThera SC, with an objective response rate (proportion of patients whose cancer shrinks by over 50%) of 90.5% for SC and 84.4% for IV.

Roche has applied to the European Medicines Authority (EMA) for an updated licence to allow NHL patients in the UK to receive MabThera SC.

MabThera IV is the standard treatment for NHL. In MabThera SC the drug is combined with the human enzyme hyaluronidase, which temporarily increases the penetrability of the tissue layer under the skin, allowing rapid absorption.

Dr Andrew Davies, Consultant in Medical Oncology at the University of Southampton, said: “This is a new formulation of a drug we are very familiar with and have been using for many years. In Southampton, we have observed a high degree of patient preference and satisfaction with this new formulation of rituximab.”

NHL is one of the most common cancers in elderly people; over 12,200 people are diagnosed with it each year in the UK.

Halozyme has four technology partnerships involving the use of hyaluronidase to facilitate SC injections. Its partnership with Roche has also produced an SC version of Herceptin.

The company’s other partnerships to exploit this technology are with Baxter Healthcare, ViroPharma and Intrexon.

Two deaths of participants in a clinical trial of chemotherapy drug bleomycin have been judged the result of culpable medication error.

The family of Gareth Kingdon (39) have won a six-figure compensation payment from University College London Hospital (UCLH).

The out of court settlement follows a similar payment to the family of Gary Foster, 27, in 2010.

Both deaths occurred during the multicentre TE23 trial, funded by the Medical Research Council, to compare the treatment of advanced testicular cancer by five chemotherapy drugs (instead of the standard three drugs) in 18 patients.

In both cases, the cause of death was an accidental overdose of bleomycin, causing lung damage.

Bleomycin was first launched by BMS in the 1970s and is now available in generic form from Teva and other companies.

Gareth Kingdon died in December 2006 after being administered the planned dosage of the drugs. However, lawyers representing his family claimed that clinicians at the hospital failed to respond to signs of lung damage.

Gary Foster died in October 2007 after being mistakenly administered twice the planned dosage of bleomycin.

In both cases, a General Medical Council panel found the investigators guilty of failing to safely implement the trial or follow trial protocols.

A spokeswoman for the Royal Marsden NHS Foundation Trust claimed the settlement was made on “a substantially discounted litigation risk basis”, since “it was not possible to determine whether the bleomycin treatment ought to have been stopped earlier and whether this would have made any difference to the outcome.”

The trial report noted that the five-drug combination (with bleomycin) was more effective in treating advanced testicular cancer than the three-drug combination, but was more toxic.

A new chemotherapy technique that isolates the liver for treatment has been used with UK patients for the first time.

The ‘chemo-bath’ technique could allow much higher doses to be used without side-effects such as hair loss and infertility.

Experts believe the same approach could be used to treat inoperable cancers in the kidney, pancreas or even lung.

Two patients at Southampton General Hospital have been treated for metastatic liver cancer with the ‘chemo-bath’ technique, resulting in tumour reduction with minimal side-effects.

Whereas traditional chemotherapy exposes the entire body to the drug’s effects, the ‘chemo-bath’ confines almost all the dose to the targeted organ.

The organ is isolated by inflating balloons inside the proximal and distal blood vessels before the drug is injected; the drug is then filtered out of the organ before the circulation is restored.

Radiologist Dr Brian Stedman (pictured) said: “To cut off an organ from the body for 60 minutes, soak it in a high dose of drug and then filter the blood almost completely clean before returning is truly groundbreaking.

“Previously, the outlook for patients specifically suffering from cancer which has spread to the liver has been poor because standard chemotherapy’s effect is limited by the unwanted damage the drug causes to the rest of the body.”

Dr Stedman said that although the technique was “in its infancy” and may need further refinement, it holds out the prospect of application to a number of organs where metastatic tumours are inoperable.

The technique is being tested in other EU countries and in the US.

NICE has reversed its opinion on the use of Bristol-Myers Squibb’s Yervoy (ipilimumab) and Roche’s Zelboraf (vemurafenib) for the treatment of advanced malignant melanoma.

The new final draft guidance recommends the use of Yervoy in people who have received prior chemotherapy.

Zelboraf is also recommended for the treatment of unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma.

The U-turn came after both manufacturers agreed to supply the treatments at a discounted rate under the terms of separate patient access schemes with the Department of Health.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, said the updated guidance was “really good news” for patients with skin cancer.

“Vemurafenib and ipilimumab are breakthrough treatments that can potentially significantly affect prognosis for these patients and we are very pleased that the manufacturers have worked with us so that we are now able to recommend both ipilimumab and vemurafenib,” said Professor Longson.

Since the publication of the first draft guidance, which NICE failed to recommend the use Yervoy due to its £80,000 price tag, BMS provided additional data and analysis surrounding the cost-effectiveness of the drug.

Roche also supplied additional analysis on the effectiveness of the drug in relation to its clinical and cost effectiveness.