Draft guidance from NICE does not recommend Avastin (bevacizumab) for treatment of recurrent advanced ovarian cancer.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

NICE has again failed to recommend Roche’s cancer drug Avastin (bevacizumab) – this time in new draft guidance for the treatment of metastatic ovarian cancer.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Committee decided that Avastin is not a cost-effective treatment option after a consultation period, following initial draft guidance issued in December 2012.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.

Roche’s Avastin (bevacizumab) has not been recommended by NHS in draft guidance as a treatment option for advanced ovarian cancer.

Although NICE confirmed the clinical benefits of the treatment it claimed its high cost was too much to justify its use on the NHS.

Sir Andrew Dillon, NICE Chief Executive, said evidence supplied by Roche “did not show that bevacizumab justifies its very high cost and could not be recommended.”

Avastin was analysed as a treatment option in women whose cancer had returned six months or more after initial treatment with platinum-based chemotherapy.

Ovarian cancer is among the top five most common cancers in women in the UK. In 2010, there were more than 7,000 new cases diagnosed.

NICE’s Appraisal Committee found Avastin may help the delay of cancer in patients for a limited time. But determined its cost was too much to expect the NHS to pay.

“We understand there are limited treatment options available to women with recurrent advanced ovarian cancer and it is always disappointing when we are not able to recommend a treatment,” said Sir Andrew. “However, it is important to remember that there are other treatments already available in the NHS for treating this condition.”

NICE has failed to recommend the use of Roche’s Avastin (bevacizumab) as a treatment option for advanced ovarian cancer in draft guidance.

The Institute’s independent Appraisal Committee concluded the drug was not a cost-effective option for the NHS after analysing data from two separate studies.

Sir Andrew Dillon, NICE Chief Executive, said Roche provided “no evidence to show that the clinical benefit of the treatment justifies its cost, when compared to existing treatments”.

The appraisal considered whether Avastin should be recommended when used with paclitaxel and carboplatin in women with advanced forms of the disease.

NICE analysed evidence from clinical trials from the licensed dosage of Avastin and the lower dosage, which is routinely prescribed in UK clinical practice.

Avastin, in combination with paclitaxel and carboplatin, was found, in certain cases, to delay the spread of cancer but NICE added there were concerns over “inconsistencies” in the data supplied by Roche.

“Although it was acknowledged that Avastin, when used in combination with paclitaxel and carboplatin, appears to provides benefit to some patients by delaying the spread of their cancer, it was unclear whether this translated into an overall survival benefit,” said Sir Andrew Dillon.

The Scottish Medicines Consortium (SMC) has not recommended Roche’s Avastin (bevacizumab) for the treatment of women with advanced ovarian cancer.

The SMC raised concerns about the economic analysis presented by Roche, despite clinical data showing significantly increased progression free survival when compared with existing options.

Dr Nicholas Reed, Consultant in Clinical Oncology at the Beatson Oncology Centre, Glasgow, said the decision was “extremely disappointing” to oncologists and denies patients “a clinically active and effective drug.”

Avastin, Roche claim, is the first treatment in 15 years to improve outcomes for women with the disease and can help progression by up to six months when compared to chemotherapy alone.

Roche said the decision not to recommend the drug reinforces that fact that Scottish patients are three times less likely to get access to innovative cancer treatments than patients south of the border.

“The Scottish Government must act to prevent Scotland falling further behind England in access to innovative cancer drugs that address an unmet medical need and clearly benefit patients, or face a negative impact on clinical research as well as increasing difficulties in recruiting and retaining the best clinicians,” said John Melville, General Manager, Roche UK.

Since its updated license to treat ovarian cancer in January 2012, Avastin has been made available to patients in England via the Cancer Drugs Fund.

It’s estimated that around 330 women with advanced ovarian cancer in Scotland could benefit from the use of Avastin each year.

NICE has confirmed its decision not to recommend metastatic breast cancer treatment Avastin (bevacizumab) in final guidance.

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

But NICE has remained consistent in its opinion through the appraisal process that Avastin is not a cost-effective first-line treatment option for use on the NHS.

Sir Andrew Dillon, NICE Chief Executive, said NICE was unable to recommend a treatment that has not been shown to work as well as existing treatments and costs much more.

“I understand this news will be disappointing to people, especially those with breast cancer that has spread elsewhere in their body,” he said. “However, NICE recommends a range of treatments that the NHS can use to treat metastatic disease and these are outlined in our clinical guideline on the diagnosis and treatment of advanced breast cancer.”

Manufacturer Roche had reacted angrily to NICE’s recommendation in an earlier stage of the appraisal process. It claimed NICE had a “lack of belief in a biologically plausible explanation for why Avastin works so well”.

The Swiss-based company also accused the Institute of ignoring progression free survival data and overall survival benefits of the drug in favour of review figures in the context of the entire population of women with the disease.

However, despite the claims NICE said it did not receive any objections to its recommendation throughout the whole appraisal process.

The SMC also recently failed to approve the use of Avastin for use within NHS Scotland for the same indication.

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 controversy over whether Avastin can replace Lucentis as a treatment for wet AMD has intensified following the publication of a major clinical study.

The CATT study, a head-to-head comparison of the two injectable drugs, suggests that Avastin is comparable to the more expensive Lucentis in terms of clinical efficacy.

However, the study also highlights that Avastin may increase the risk of major adverse events such as blood clots and congestive heart failure.

Roche’s Avastin (bevacizumab) is not licensed for treatment of the eye disorder wet AMD, which affects many elderly people, in Europe or the USA.

However, its off-label use has become widespread because it is much cheaper than the standard treatment, Roche’s Lucentis (ranibizumab) – which is marketed outside the US by Novartis.

In the UK, Lucentis (which costs £890 per dose) is the only NICE-approved treatment for wet AMD, but some PCTs recommend the use of Avastin (at £50–100 per dose) to save money.

Novartis is currently seeking a judicial review of the recommendation of Avastin for wet AMD by one PCT cluster.

The two-year Comparison of Age-related macular degeneration Treatment Trials (CATT), carried out by the National Eye Institute in the US, has concluded that both drugs offer “robust and lasting” improvements in vision.

However, those patients taking Avastin show a higher incidence of serious adverse events (40%) than those taking Lucentis (32%). The high figures reflect the median age (over 80) of the study participants.

The adverse events recorded include arterial and venous blood clots, haemorrhagic stroke, congestive heart failure and vascular death

The study authors concluded: “The choice of drug and dosing regimen for patients must balance the comparable effects on vision, the possibility of true differences in adverse events, and the fortyfold difference in cost per dose.”

However, Novartis has drawn attention to the adverse event data, arguing that “it would be inappropriate to advocate use of unlicensed bevacizumab for wet AMD, on the basis of these trials,” and further noting that of the two drugs, only Lucentis was specifically designed for use in the eye.

NICE has failed to recommend Roche’s Avastin (bevacizumab) for the first-line treatment of metastatic breast cancer after raising a number of uncertainties over its use in new draft guidance.

Its independent Appraisal Committee questioned the clinical benefit of the drug in overall survival and concluded its high cost was not a good use of NHS resources.

Sir Andrew Dillon, NICE Chief Executive, says the evidence provided “did not conclusively” demonstrate Avastin to be clinically and cost effective.

The breast cancer drug was being appraised when used in combination with the chemotherapy drug Xeloda (capecitabine).

Data provided by Roche had demonstrated that median progression-free survival benefit associated with Avastin plus Xeloda was 2.9 months greater than Xeloda monotherapy alone.

However, the Committee claimed it was unclear whether that benefit translated into an improvement in overall survival.

The Committee also raised the issue of a lack of data showing whether patients would have a better quality of life than if they were treated with chemotherapy alone.

Also, NICE noted that Roche’s cost-effectiveness figures were based on a specific subgroup of patients who had previously received a taxane, and not on the whole capecitabine cohort.

Given these uncertainties the Committee concluded it was not possible to arrive at a plausible Incremental Cost Effectiveness Ratio (ICER) per QALY gained for bevacizumab plus capecitabine compared with capecitabine alone for the whole patient population and were not able to recommend the treatment.

“We can’t recommend a drug that has not been shown to work as well as, or better than, current treatments and costs much more,” said Sir Andrew. “We want to ensure people have access to the best treatments the NHS can afford; bevacizumab has so far not been proven to be clinically or cost-effective.”

Breast cancer is one of the most common cancers in England. In the UK, it is estimated that more than 48,000 women and around 300 men are diagnosed with the disease each year.

The draft guidance is now open for consultation.