Draft guidance from NICE does not recommend Avastin (bevacizumab) for treatment of recurrent advanced ovarian cancer.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NICE draft guidance does not recommend Afinitor (everolimus), a treatment for advanced breast cancer that can increase progression-free survival by four months.

The Novartis drug, described by charity Breakthrough Breast Cancer as “one of the biggest advances in breast cancer treatment in many years”, does not meet NICE’s criteria for an ‘end of life treatment’.

The decision will heighten concern over NICE’s QALY metric for value, which the European Commission recently declared to be scientifically invalid.

Afinitor, an oral formulation of everolimus (which is already widely used as an immunosuppressant), is licensed for use in post-menopausal women with advanced HER-2 negative breast cancer, which will not respond to Herceptin.

The drug inhibits the division of tumour cells and the growth of blood vessels around a tumour, thereby inhibiting tumour growth and metastasis.

Clinical trial results published in September 2012 found that Afinitor could ‘stall’ advanced breast cancer by four to five months.

Dr Rachel Greig of Breakthrough Breast Cancer said: “Everolimus is one of the biggest advances in breast cancer treatment in many years.”

Though “by no means a cure,” she commented, “it could give patients several extra months of good quality of life with their families.”

Sir Andrew Dillon, NICE’s Chief Executive, explained: “While the independent Appraisal Committee acknowledged that everolimus may offer a step change in treatment by restoring sensitivity of the tumour to hormone therapy, the evidence highlighted uncertainty relating to how much the treatment extends overall survival.”

The failure to extend overall survival was only considered crucial because Afinitor did not meet NICE’s criteria for an ‘end of life drug’, since its target patients had a life expectancy slightly over two years.

Consultation on the draft guidance will remain open until 22 April 2013.

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.

Cell Therapeutics has gained conditional authorisation from the European Commission to market its treatment for non-Hodgkin’s B-cell lymphoma.

The US biopharma company will be able to market Pixvuri (pixantrone) through a named patient programme in the EU.

This type of authorisation allows a company to quickly market a drug that addresses a major unmet medical need, while waiting for full approval.

According to Cell Therapeutics, the decision follows a phase III clinical trial that showed Pixvari to offer longer progression-free survival and a higher rate of complete response than chemotherapy.

Cell Therapeutics plans to commercialise Pixvari in Europe in the second half of 2012, and will need to complete a post-marketing study to confirm the drug’s clinical efficacy.

The EC decision is a breakthrough for the product, which was rejected by the FDA in 2011 on the grounds that its benefits were unproven. The company is preparing for a second FDA committee review.

Roche intends to submit its new T-DM1 breast cancer drug for EU and US approval this year following its successful phase III trial.

The biotech giant said its ‘armed antibody’ drug candidate, which combines the active agents of Herceptin and a chemotherapy drug, showed better progression-free survival data than a combination of Tyverb and Xeloda.

T-DM1, developed by Roche in partnership with ImmunoGen, is considered a potential successor to Roche’s blockbuster breast cancer drug Herceptin, which faces completion from biosimilars in 2015.

Herceptin has been approved in the EU for treatment of Her2-positive breast cancer, an aggressive type of cancer linked to a particular gene variant.

T-DM1 combines the antibody trastuzumab from Herceptin with the agent DM1from the chemotherapy drug maytansine.

Roche said that according to the EMILIA trial results, Her2-positive breast cancer patients showed longer progression-free survival than a combination of two major existing products: GSK’s Tyverb and Roche’s Xeloda.

In addition, it caused less side-effects (such as hair loss and reduced white blood cell count) than Herceptin alone, as well as offering the convenience of a combined medication.

The overall survival rates from the EMILIA trial are likely to become available by 2014.

Roche anticipates that T-DM1 will successfully rival generic versions of Herceptin and newer branded medications such as Tyverb.

The European Medicines Agency (EMA) has published draft guidelines on the assessment of stratified medicine for cancer, including the use of biomarkers and companion diagnostics.

The proposed changes reflect the growing relationship, both clinical and commercial, between genetic analysis and the development of drugs (such as Herceptin) that target patients with a specific genotype.

The revised EMA guidelines on Evaluation of Human Anticancer Medicines guidelines include new disease-specific guidance on lung cancer and prostate cancer and revised guidelines on blood cancers.

They also emphasise the value of exploratory studies to establish the “technical/quantitative reliability” of biomarkers, and to maximise the application of companion diagnostics.

In addition, the methodology of phase III trials using progression-free survival or disease-free survival as a key outcome is reviewed.

The Evaluation of Human Anticancer Medicines guidelines were first adopted in 1996. They cover all stages of clinical drug development for the treatment of cancers. Disease-specific guidance was introduced in 2010.

The consultation on the revisions will run until May 31, 2012.