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appraisal of Avastin (bevacizumab) after it was not recommended as a first line treatment for advanced breast cancer in draft guidance.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.

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(trastuzumab) with aromatase inhibitors as a first line treatment for a particular type of breast cancer in final draft guidance.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

NICE has again failed to recommend the use of Eisai’s breast cancer drug Halaven (eribulin) after further questioning the treatment’s side-effects in new guidance.

Eisai had provided additional data after NICE’s original decision not to recommend the treatment back in November.

But NICE concluded the data, which analysed women previously treated with Xeloda (capecitabine), did not show “robust” survival advantage and decided there no “convincing cost effectiveness” for its use.

The Institute received one appeal on its earlier draft guidance. This was dismissed on all counts; however, the Appeal Panel did recommend that sections describing the adverse events experienced with the drug and its comparator were revised.

Halaven has been shown to potentially extend the life of women by 2.7 months compared with a ‘treatment of physician’s choice’. However, the cancer drug did not fulfil all of NICE’s end-of-life criteria.

Sir Andrew Dillon commented: “Although the evidence presented to the independent Advisory Committee indicated that eribulin may help some patients live for a little longer, it also caused more undesirable side effects than other treatments already available, and the committee felt that eribulin’s effects on health-related quality of life had not been adequately assessed.”

NICE’s Chief Executive added that the Committee heard from practising clinical experts who told the Institute that patients usually receive sequential treatment with Navelbine (vinorelbine), Xeloda and infrequently Gemzar (gemcitabine).

But Sir Andrew said that experts “stressed” that if Halaven were to be recommended it would “be unlikely” to replace existing treatments “because of its related side-effects”.

Common adverse effects of the treatment include fatigue, alopecia, peripheral, neuropathy, nausea, neutropaenia, leukopaenia and anaemia.

Eisai have again claimed they are “dismayed” at the decision and accused NICE of “not giving enough support to women” and the “physicians who want to treat them”.

Nick Burgin, European Director of Market Access, said: “We hope that NICE grant a rapid re-review as new data is constantly emerging that will help inform their decision.”

Despite the lack of NICE recommendation, Halaven is available through the Government’s Cancer Drugs Fund and is one of the top twelve drugs prescribed through the system.

On the same day as the final NICE guidance, Eisai signed a partnership deal with Valeant Pharmaceuticals to promote and distribute Halaven in eight central and eastern European countries.

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.

Final guidance by NICE does not recommend the use the AstraZeneca’s breast cancer drug Faslodex (fulvestrant) after it was decided it would not be an effective use of NHS resources.

NICE concluded that the treatment does not work significantly better than existing options available to women who have oestrogen-receptor-positive, locally advanced or metastatic breast cancer.

Sir Andrew Dillon, NICE Chief Executive, says Faslodex’s “effectiveness is uncertain” when compared to preferred treatment options on the NHS.

Faslodex has a marketing authorisation as an alternative to aromatase inhibitors for postmenopausal women who have oestrogen-receptor-positive, locally advanced or metastatic breast cancer, and who have already received anti-oestrogen therapy.

AstraZeneca estimates that its treatment could extend life when compared to using the aromatase inhibitors currently prescribed on the NHS, anastrozole and letrozole. However, NICE’s independent Appraisal Committee believed these estimates to be considerably uncertain.

The Committee concluded that it had not been supplied with any conclusive evidence that demonstrated that Faslodex extends life or delays tumour progression any more than aromatase inhibitor therapy.

It also decided that the medication did not fulfil all of NICE’s end-of-life-criteria because the CONFIRM trial showed that Faslodex is indicated for women who have a life expectancy greater than 24 months.

Sir Andrew Dillon said while there was evidence that Faslodex can delay the growth of breast cancer NICE has to be certain of its benefits. “Confidence about the additional benefits new treatments bring is important both for patients and for those who have responsibility for managing the resources available to the NHS,” he said.

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.

NICE has failed to recommend the use of breast cancer drug Halaven (eribulin) in final draft guidance after raising concerns over the side effects of the treatment.

Its independent Advisory Committee indicated the medication may help patients live longer but, when compared to existing treatments, there were more  “undesirable side effects”.

Draft NICE guidance does not recommend the routine use of AstraZeneca’s anti-oestrogen drug Faslodex (fulvestrant) in the NHS to treat certain types of breast cancer.

Faslodex was authorised in 2010 for marketing as an alternative to aromatase inhibitors to delay the growth of oestrogen-receptor-positive, locally advanced or metastatic breast cancer in postmenopausal women who have already received anti-oestrogen therapy (such as tamoxifen).

NICE’s Independent Advisory Committee has concluded that the drug is not significantly more effective than existing treatments, and so its routine use would not be a good use of resources.

The Committee judged AstraZeneca’s claim that Faslodex could extend life relative to the aromatase inhibitors anastrozole and letrozole to be uncertain as network meta-analyses showed no statistically significant differences.

In addition, they found that Faslodex delayed cancer growth more effectively than anastrozole but not more so than letrozole. An incremental cost effectiveness ratio of £35,000 per QALY gained for Faslodex 500mg compared with anastrozole was estimated, but with “considerable uncertainty”.

The draft guidance thus recommends that NHS doctors should not prescribe Faslodex as an alternative to aromatase inhibitors in relevant cases – but that women who are currently receiving Faslodex should be able to continue to do so until they and their doctors decide to stop.

Sir Andrew Dillon, Chief Executive of NICE, commented: “While there is evidence that fulvestrant can delay the growth of breast cancer, our independent committee found that when used according to its marketing authorisation, its effectiveness is uncertain compared to aromatase inhibitors, which are currently the preferred treatment options on the NHS.

“As fulvestrant has not been proven to be cost-effective, we cannot justify diverting NHS funds from other areas of healthcare in order to fund its use.”

The draft guidance is open to appeal until 24 November. NICE hopes to publish final guidance in January 2012.

Eisai has revealed its surprise over NICE’s decision not to recommend its breast cancer drug Halaven (eribulin) in draft guidance.

NICE raised worries over the side-effects Halaven caused and the data supplied by Eisai which compared the drug with a ‘treatment of physician’s choice’ (TPC).

But Nick Burgin, European Director of Market Access, Eisai, says NICE’s “unwillingness” to recommend the treatment comes as a “real surprise”.

Eisai say the side-effect profile of Halaven was “expected and manageable”, and that serious adverse events and adverse events leading to therapy discontinuation actually occurred more in those on TPC than its injection.

The draft guidance is based on Phase III data which showed a median overall survival benefit of 13.1 months for patients receiving Halaven, compared to 10.6 months for those using a TPC. Before its approval in Europe, Eisai claims that no single treatment demonstrated a “statistically significant prolongation of median overall survival” than its clinical trial.

“We are hugely disappointed with the draft guidance issued by NICE,” said Nick Burgin. “It has not recommended an innovative treatment for a vulnerable group of women with heavily pre-treated locally advanced or metastatic breast cancer, with a proven overall survival benefit.”

Halaven is approved in the EU, USA, Switzerland, Japan, and Singapore. It was launched in the UK in April 2011 and Eisai say that patients have already started to benefit from the treatment.

A Patient Access Scheme had also been agreed with DH making the price of Halaven in the UK the lowest in the world. The ABPI says the example of Halaven highlights the need to switch to a value-based pricing approach to improve access of medicines to patients.

“There is serious concern in the research-based pharmaceutical industry about delay in new and innovative medicines reaching patients which potentially denies access to proven effective drugs for urgent clinical needs,” a statement said.

“The UK has amongst the lowest prices in Europe for our medicines but our uptake is both slow and low. The new pricing and reimbursement system needs to reduce bureaucracy and get the right medicines to patients as quickly as possible.”