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(trastuzumab) with aromatase inhibitors as a first line treatment for a particular type of breast cancer in final draft guidance.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.

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.”

Pharma giant Roche has gained an EU approval for one of its breast cancer drugs and lost a US approval for another.

The EMA has recommended Herceptin (trastuzumab) for a licence extension that would see the drug used earlier in the progression of breast cancer.

In the same week, the FDA has revoked its approval for Roche’s Avastin (bevacizumab) as a treatment for breast cancer on the grounds that its benefits are outweighed by its side-effects.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) has backed the use of Herceptin to treat patients with HER2-positive early breast cancer.

The drug is indicated for use in combination with neoadjuvant chemotherapy, followed by adjuvant Herceptin therapy.

The CHMP recommends the drug for use where the cancer is locally advanced or where tumours are larger than 2cm in diameter.

Herceptin is already approved in the EU for metastatic HER2-positive breast cancer. The drug works by reducing the body’s production of HER2, a growth factor that increases the aggressiveness of breast tumours.

The FDA has revoked its former approval for Roche’s breast cancer drug Avastin on the grounds that its benefits are modest and do not outweigh its side-effects. This follows the FDA’s decision in July to revoke Avastin’s approval in metastatic breast cancer.

The risks of Avastin include severe hypertension, bleeding, heart attack, heart failure and membrane perforations, the FDA said.

FDA Commissioner Margaret Hamburg commented: “After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit.”

Roche plans further studies to identify subgroups of advanced breast cancer patients who may benefit from treatment with Avastin, particularly in combination with paclitaxel.

Avastin will remain on the US market for other indications, including colon, lung, kidney and brain cancers.

The drug is currently approved in Europe for use in combination with paclitaxel to treat breast cancer.

Roche’s cancer drug Herceptin (trastuzumab) will soon be available to treat NHS patients with gastric cancer, after NICE reversed its previous negative recommendation.

The Institute has recommended the drug for patients with metastatic gastric cancer who have high levels of human epidermal growth factor receptor 2 (HER2), a protein found on the surface of some cancer cells.

Despite originally rejecting Herceptin in this patient population, NICE reconsidered its guidance based on a new analysis provided by Roche which focused on patients with the highest levels of HER2.

Herceptin use will be restricted to the treatment of people who have not received prior treatment for their metastatic disease and whose tumours express high levels of HER2, and in combination with cisplatin and capecitabine or 5-fluorouracil, for

Andrew Dillon, Chief Executive of NICE said: “The Committee discussed this new information and concluded that trastuzumab was cost-effective in this patient group. The Committee also agreed that trastuzumab for this group of patients fitted the criteria for consideration for appraising a life-extending, end-of-life treatment.”

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