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appraisal of Avastin (bevacizumab) after it was not recommended as a first line treatment for advanced breast cancer in draft guidance.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 use of combination therapies in the treatment of cancer patients is set to increase in the future, according to a new report.

Analysis found that oncological treatments are evolving to include biologic medication, which, in combination with cytotoxic drugs, is rapidly becoming the top pharmaceutical therapy.

GBI Research’s report found the effective capabilities of biologics in controlling and treating complications has led to their widespread use and popularity amongst patients and prescribers.

The cytotoxic therapies markets has eight major indications and brands include Taxotere (docetaxel), Alimta (pemetrexed) and Xeloda (capecitabine) – all of which have exceeded sales of $1 billion.

However, these drugs are set to be exposed to generic competition in coming years which will reduce the cost of combinational treatments.

The popularity of such treatments is also expected to convince pharmaceutical companies to apply for label extensions on their existing biologics portfolio for multiple oncology complications.

This, the report said, will support the continued development of cytotoxic drugs in the future, despite significant safety hurdles that have previously led to weak pipelines.

The cytotoxic therapies market accounted for $6.5 billion in revenue ten years ago. It grew at an annual rate of 5.8% to reach $10.1 billion in 2010. The report now expects generic competition to reduce revenues in the market by 2017 to $7.6 billion – despite predicted uptake.

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.

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.

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.

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.”

NICE has issued final guidance to the NHS not recommending the use of Erbitux (cetuximab), Avastin (bevacizumab) and Vectibix (panitumumab) for the treatment of metastatic colorectal cancer that has progressed after chemotherapy.

Concerns were raised by NICE’s Appraisal Committee surrounding the clinical evidence of the products, especially the use of Avastin.

Sir Andrew Dillon, NICE Chief Executive, says the Institute is “disappointed” not to be able to add the three drugs to the six other recommended options available to the NHS.

No appeals were received on the final draft guidance which did not recommend the treatments after the evidence was considered.

Uncertainness were raised over the data supplied by Roche on Avastin plus non-oxaliplatin chemotherapy of its overall survival gain when used as a second or third-line treatment for those who had not responded to first-line or second-line chemotherapy.

Similar queries were also asked by the Committee of the estimates supplied by Merck Serono on Erbitux plus Campto based on the mixed treatment comparison, and on the magnitude of the survival benefit of Vectibix relative to best supportive care provided by Amgen.

“We have to be confident that the benefits that drugs offer patients really do justify what the NHS will have to pay for them,” said Sir Andrew.

“The independent appraisal committee which drafted the recommendations does not feel it has enough evidence, especially in the case of bevacizumab, to feel confident in recommending these drugs for use on the NHS.”

Campto (irinotecan), Eloxatin (oxaliplatin), Xeloda (capecitabine), tegafur with uracil and Erbitux (cetuximab) have all previously been recommended for various stages of colorectal cancer for use on the NHS.

NICE has failed to recommend a trio of drugs for the treatment of metastatic colorectal cancer that has progressed after first-line chemotherapy in final draft guidance.

Its independent Appraisal Committee deemed there was not enough evidence to recommend the use of Erbitux (cetuximab), Avastin (bevacizumab) and Vectibix (panitumumab).

Sir Andrew Dillon, NICE Chief Executive, said the Institute has to be confident that the benefits that treatments offer to patients justify what the NHS has to pay for them.

Campto (irinotecan), Eloxatin (oxaliplatin), Xeloda (capecitabine), tegafur with uracil and Erbitux (cetuximab) have all previously been recommended for various stages of colorectal cancer.

Uncertainness were raised over the evidence presented by Roche on Avastin plus non-oxaliplatin chemotherapy of its overall survival gain when used as a second or third-line treatment for those who had not responded to first-line or second-line chemotherapy.

Questions were also asked by the Committee of the estimates supplied by Merck Serono on Erbitux plus Campto based on the mixed treatment comparison and on the magnitude of the survival benefit of Vectibix relative to best supportive care provided by Amgen.

“We have already recommended six treatments for various stages of colorectal cancer and are disappointed not to be able to add these three drugs, cetuximab, bevacizumab and panitumumab to the list of treatments for this stage of the disease,” said Sir Andrew.

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”.