NICE draft guidance does not recommend Afinitor (everolimus), a treatment for advanced breast cancer that can increase progression-free survival by four months.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Consultation on the draft guidance will remain open until 22 April 2013.

A new Tumour Profiling Unit at the Institute of Cancer Research (ICR) in London will spearhead research into ‘personalised’ medicine and drug resistance in cancers.

The new research centre, the largest of its kind in the NHS, will analyse tumour cell DNA to pinpoint the critical mutations that cause cancer.

The aim is to develop many ‘personalised’ drugs, such as Herceptin, that can attack cancers with a specific genetic characteristic.

Tumour samples from patients at the Royal Marsden Hospital will be repeatedly tested to identify the genetic mechanisms underlying tumour development and drug resistance.

The Tumour Profiling Unit will also store the genetic codes of cancer patients, and make the findings available to doctors and pharmaceutical companies.

Professor Alan Ashworth, the ICR’s Director, said: “None of this is science fiction. This is now happening. We think we’re pioneering the clinical application of this by setting up the Tumour Profiling Unit, but one would think this would be absolutely routine practice for every cancer patient – and that’s what we’re aiming to bring about.”

Professor Ashworth compared cancer treatment to the game ‘Whack-a-Mole’: every time a cancer drug is successful, tumours develop resistance to it. The new research unit aims to find treatments that can stop the cancer evolving.

According to a recent DH announcement, the entire genetic code of up to 100,000 NHS patients with cancer and rare diseases will shortly be sequenced to facilitate research.

NHS uptake of NICE-approved medicines varies according to location and disease area, according to the Health and Social Care Information Centre (HSCIC).

The HSCIC report shows that for 13 disease areas where comparison was possible, use of NICE-approved drugs was above the expected level in six and below it in six.

Roche’s cancer drug Herceptin (trastuzumab) was among several medicines whose prescription level was lower than expected.

Comparisons between NHS organisations indicate regional variation.

However, HSCIC Chief Executive Tim Straughan said: “Anyone interpreting the figures needs to be clear about the limitations of what the data show and it would certainly be wrong to think they definitively show drugs are being either ‘under’ or ‘over’ prescribed.”

Medicines whose uptake was higher than expected included carmustine implants and temozolomide (for brain cancer), varenicline (for smoking cessation), insulin glargine and detemir (for type 1 diabetes), statins (for high cholesterol) and drugs for osteoporosis.

Medicines whose uptake was lower than expected included riluzole (for MND), naltrexone (for heroin addiction), trastuzumab (for breast and gastric cancer), prucalopride (for chronic constipation), febuxostat (for gout) and drugs for acute coronary syndrome.

Steve Oldfield, Managing Director UK & Ireland of Sanofi, commented: “Many of the medicines appraised by NICE which are absent from the report are not reaching patients as quickly as they should, as local funding pressures in the NHS start to bite.

“More worryingly still, the very latest medicines launched in the last two years are being used significantly less than expected.”

NICE has failed to recommend GSK’s Tyverb (lapatinib) or Roche’s Herceptin (trastuzumab) with aromatase inhibitors as a first line treatment for a particular type of breast cancer in final draft guidance.

The decision is based on uncertainties over the overall survival benefits compared to existing treatments of both medicines and the high cost of the treatments.

Sir Andrew Dillon, Chief Executive of NICE, said that while the two have been shown to reduce the growth and spread of breast cancer the extent of overall survival extension “appears to be small or difficult to quantify”.

Final guidance on the appraisal is now expected in June.

The guidance only advises the use of the drugs alongside aromatase inhibitors as a first line treatment option to delay the growth of advanced breast cancer that has spread and reacts with oestrogen or progesterone and has high levels of HER2.

Alongside the clinical benefits, NICE also raised concerns around the cost effectiveness of both products. GSK estimates that the most plausible incremental cost effectiveness ratio (ICER) for Tyverb is likely to be around £74,400 per QALY gained. Roche estimates the most plausible ICER for Herceptin to be around £51,000 per QALY gained – both far in excess of the £20,000-£30,000 NICE typically deems to be a cost effective use of NHS resources.

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.

An easily injectable formulation of Roche’s breast cancer drug Herceptin has been shown to be as safe and effective as the intravenous version now available.

The new version of Herceptin (trastuzumab), available via subcutaneous (SC) injection, reduces the drug’s administration time from 30 to five minutes.

UK patients who are eligible for the SC formulation could be treated more rapidly, freeing up capacity in hospital chemotherapy facilities.

The HannaH trial compared Herceptin SC with Herceptin IV in 596 women with untreated HER2-positive early-stage breast cancer.

The study met its primary endpoint of ‘non-inferiority’ for pharmacokinetics and success in tumour eradication, and there were no new safety concerns.

Breast cancer is the most common cancer in the UK, with more than 48,000 newly diagnosed patients and 12,000 fatalities in 2008.

Herceptin is a targeted drug that blocks the function of HER2, a protein produced by a gene with cancer-causing potential. It uses the body’s immune system to destroy the tumour cells.

In 15% of women with breast cancer, increased quantities of the HER2 receptor are present on the tumour cells. HER2-positive breast cancer is associated with relatively poor survival rates.

Herceptin is indicated in Europe for the treatment of early-stage and metastatic breast cancer and metastatic gastric cancer. It is currently approved in an IV formulation only.

Herceptin SC uses a specialised technology to break down the skin barrier to drugs, enabling the subcutaneous injection of large volumes of medication.

Dr Mark Verrill, Consultant Medical Oncologist at Freeman Hospital, Newcastle Upon Tyne, commented: “The result of the HannaH trial is good news, particularly for patients. Herceptin is the standard of care, so the ability to deliver the drug in approximately five minutes without the need to secure intravenous access makes the treatment far more convenient.

“Aside from the benefit for patients, Herceptin SC has the potential to ease capacity at busy chemotherapy day units and may facilitate treatment close to home, resonating with the Cancer Reform Strategy.”

Roche is the world’s largest biotechnology firm, specialising in the development of personalised medicines for oncology, virology, inflammation, metabolism and CNS disorders.

NICE has failed to recommend GSK’s Tyverb (lapatinib) or Roche’s Herceptin (trastuzumab) with aromatase inhibitors as first-line treatments for women with breast cancer in a second draft guidance.

Questions were again raised about the cost and effectiveness of both treatments when compared against existing options to delay the growth of advanced breast cancer that has already spread to other parts of the body, and for patients whose tumour cells react with oestrogen or progesterone and have high levels of HER2.

Sir Andrew Dillon, Chief Executive of NICE said that independent analyses indicate that both treatments “do not appear to be cost effective for the NHS” due to “uncertain clinical benefits”.

The second draft guidance follows an appeal from Roche against NICE’s independent Appraisal Committee and its initial findings published in July 2011. The Committee concluded that Herceptin did fulfil the small population criterion within NICE’s “end of life criteria”. This decision was subject to appeal, but upheld by an independent panel in November 2011.

Experts estimate that between 50 and 2,000 postmenopausal women are diagnosed with this type and stage of breast cancer each year. It is believed that the majority of these women are likely to be offered Herceptin as a first-line treatment option.

Tyverb and Herceptin would only usually be considered as first-line options alongside aromatase inhibitors when chemotherapy is deemed unsuitable – but it is unclear how many patients this would be relevant to.

“Having reviewed the available evidence, our committee of experts has found that while both lapatinib and trastuzumab can reduce the growth and further spread of metastatic breast cancer tumours when taken alongside the aromatase inhibitors letrozole and anastrozole, the extent that these treatments can improve overall survival appears to be small or undefined,” said Sir Andrew.

The Scottish Medicines Consortium (SMC) also failed to recommend the use of Tyverb or Herceptin for use on the NHS in Scotland for this particular type and stage of breast cancer when it recently published advice.

NICE’s draft guidance has now been issued for consultation. The deadline for comments to be received is Tuesday 6^th March. The independent Appraisal Committee will then meet to review any submissions.

Roche saw Group sales fall 10% in Swiss francs (CHF) to 42.5 billion in 2011 due to the appreciation of the franc, and revenue decrease by 12% in its Pharmaceuticals Division after sales of Avastin and Tamiflu fell.

Pharmaceutical sales accounted for 32.7bn CHF after MabThera generated 6bn CHF (+8%), Herceptin 5.2bn CHF (+9%) and sales of Lucentis increased by 23% to 1.5bn CHF.

Severin Schwan, Roche CEO, says the Group achieved its “sales and earnings targets” in 2011 and made “significant progress with our pipeline”.

The company expects to record single-digit sales growth for the Group and its pharma division in 2012 after achieving several important regulatory milestones in Q4 of 2011.

Group sales in constant currencies were up 1% after its pharma division, excluding Tamiflu, grew at the same rate. Sales were up 2% in constant currencies in the US to 12.2bn Swiss francs and in international markets by 3% to 8.5bn. However, pharmaceutical sales in Western Europe dropped 3% to 8.2bn and in Japan by 6% to 3.8bn.

Core operating profit increased 6% in constant currencies, core earnings per share was up by 11% and net income jumped 26% to 9.5bn CHF in 2011.

Sales of cancer medicines Xeloda (1.3bn CHF; +8%), Tarceva (1.2bn CHF; +7%) and Zelboraf (31m) – recently launched in the US – were called “encouraging”. But a 7% decrease in sales of Avastin, NeoRecormon (-23%), Bonviva (-22%) and CellCept to (-14%) were put down to US health reforms, European austerity measures and Japanese biennial price cuts resulting in a negative growth impact of 295m CHF.

“With 17 positive late-stage clinical trials in 2011, we continue to build our future business with innovative products,” said Severin Schwan. “For 2012 we expect Group sales to grow at a low to mid-single-digit rate and we have set ourselves the target of high single-digit Core Earnings per Share growth.”

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.

GlaxoSmithKline’s breast cancer drug Tyverb (lapatinib) has failed to show a significant increase in disease-free survival (DFS) when used alone in patients with early-stage HER2-positive breast cancer.

The results of the TEACH phase III clinical trial mean that Tyverb (known as Tykerb in the US) is unlikely to succeed as a monotherapy in this indication, though it will continue to be used in combination therapy.

The TEACH trial established that 13% of patients treated with Tyverb following initial surgery or chemotherapy for breast cancer achieved DFS after four years, compared to 17% on placebo.

The trial did not compare Tyverb with Roche’s breast cancer drug Herceptin (trastuzumab). The two drugs were approved by the FDA for use in combination in 2007, and in that indication earned GSK $360 million in 2010.

However, whereas Herceptin has proved successful as a monotherapy, Tyverb has not. In September, GSK abandoned the monotherapy arm of another trial (ALTTO) after concluding that Tyverb was less effective in treating early-stage breast cancer than Herceptin alone.

The TEACH trial is still expected to support the use of Tyverb in combination with Herceptin.

“We are disappointed that the improvement in disease-free survival with lapatinib monotherapy in TEACH did not reach statistical significance,” said Rafael Amado, Senior VP of Oncology Development at GSK.

“Lapatinib combination therapy remains an important treatment option for patients with metastatic HER2-positive breast cancer whose disease has progressed on treatment with trastuzumab-based regimens.”