NICE Rejects Roche’s Avastin In Advanced Ovarian Cancer

The U.K.'s health care cost regulator says it wouldn't recommend Roche's Avastin as a first-line treatment for advanced ovarian cancer along with standard chemotherapy, on grounds it doesn’t offer value for money.

Draft guidance from the National Institute for Health and Clinical Excellence does not recommend using Roche’s Avastin (bevacizumab) along with paclitaxel and carboplatin for people with advanced ovarian cancer.

That’s despite the fact that current U.K. clinical practice is to prescribe bevacizumab at a dosage below that for which it is currently licensed. Avastin, in combination with carboplatin and paclitaxel was approved by the European Medicines Agency for the treatment of women with advanced ovarian cancer in December 2011.

Bevacizumab in combination with the two chemotherapies is licensed in England and Wales for people with metastatic ovarian cancer at a dose of 15 mg per kg of body weight. But many U.K. clinicians prescribe bevacizumab for this indication at an unlicensed dose of 7.5 mg/kg.

Explaining its stance, NICE in a statement said that it “is unable to make recommendations on a treatment outside of its marketing authorization.”

It’s the first time NICE has reviewed Avastin at any dosage for this indication for use by the country’s publicly-funded National Health Service, or NHS. Evidence submitted by Roche involved clinical trials using both the licensed and the commonly used unlicensed dose. NICE said this and other factors made it difficult to evaluate the clinical effectiveness of bevacizumab.

The agency’s appraisal committee concluded that the clinical trial known as GOG-0218, which assessed the licensed dose of bevacizumab, was the most relevant to its deliberations (Also see "Another Phase III Study Supports Avastin Expansion To Ovarian Cancer" - Pink Sheet, 1 Jul, 2010.). It also said there were “inconsistencies in how results were recorded” and questioned whether the trial’s “censored” or “uncensored” data would be the most appropriate to appraisal.

The trial’s uncensored and censored results relate to a blood test given to patients to check levels of CA125 in their bloodstream.

Raised levels can indicate ovarian cancer or, if someone already has the disease, a rise in CA125 levels could indicate that the disease is progressing, although it can take up to six months for this to become apparent.

The uncensored data from GOG-0218 recorded any rise in CA125 levels as evidence that a patient’s cancer had progressed. In comparison, the censored data removed any results indicating a rise in CA125 levels from further analysis. The Appraisal Committee heard that roughly one third of patients with ovarian cancer do not express CA125 and that it is not used in U.K. clinical practice as the sole marker to indicate disease progression.

NICE said the committee thus concluded that GOG-0218’s censored data for progression-free survival was most relevant to U.K. clinical practice, but added that censoring data might have introduced a bias.

NICE said when taken together the evidence “suggested the Incremental Cost Effectiveness Ratio (ICER) was likely to be between £128,000 and £161,000 per QALY [quality-adjusted life year] gained. As a result, the committee concluded it could not recommend bevacizumab as a cost-effective use of limited NHS resources.”

NICE Chief Executive Andrew Dillon echoed that, saying in a statement that “although it was acknowledged that bevacizumab, when used in combination with paclitaxel and carboplatin, did appear to provide some benefit to some patients in terms of delaying the spread of their cancer, it was unclear whether this translated into an overall survival benefit. There was no evidence to show that the clinical benefit of the treatment justifies its cost, when compared to existing treatments – an important factor to consider, especially as the NHS has finite resources.”

Roche responded with a statement saying it was “disappointed that, as part of its review, NICE did not consider the entirety of evidence that was presented to them for Avastin as a first-line treatment of advanced ovarian cancer and will continue to work with NICE to secure a positive recommendation for Avastin in this setting.”

NICE said Roche has not submitted a Patient Access Scheme to the Department of Health for this appraisal. Companies regularly offer do so to help to oil the wheels and trigger a rethink by NICE. Such schemes are agreed between the manufacturer and Department of Health to make the treatment in question more cost-effective for the NHS and characteristically involve a hefty price discount.

The reimbursement regulator’s preliminary guidance is now available for public consultation until Jan. 22, 2013. The next version of draft guidance will then be issued with final guidance on the use of bevacizumab when used with paclitaxel and carboplatin as a treatment for advanced ovarian cancer expected later next year. “Until then, NHS bodies will make decisions locally on the funding of specific treatments,” NICE said.

Around 7,000 women are diagnosed with ovarian cancer in England each year, making it the second-most-common gynecological cancer and the fifth-most-common cancer in women.

Diagnosis happens after the cancer has already spread in 75% of cases, and over 4,000 women will die from the disease each year, according to Roche.