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Avastin for colorectal cancer rejected again in UK; Erbitux stands to gain

Wednesday, November 25, 2009, 21:12 This news item was posted in Pharma category and has 0 Comments so far.

Avastin, the much-hyped block-buster anti-cancer therapy from Roche has been rejected by as treatment against colorectal cancer.

Avastin has been rejected by a second time by the National Institute for Health and Clinical Excellence (NICE), the UK’s cost effectiveness watchdog,  in combination with chemotherapy for first-line colorectal cancer patients.

Avastin isn’t a cost effective use of NHS resources, NICE argued.

Avastin’s costs per quality-adjusted life year gained overshot its GBP30,000 threshold in the first-line metastatic colorectal cancer (CRC) setting, estimated an appraisal committee at NICE before providing a negative decision.

Preliminary recommendations published estimated that Avastin plus XELOX (capecitabine, oxaliplatin) as a first-line CRC treatment produced an incremental cost effectiveness ratio of GBP36,400 per QALY compared to XELOX alone.

Similarly, Avastin and FOLFOX (leucovorin, 5-fluorouracil, oxaliplatin) resulted in an ICER of GBP31,500 compared with FOLFOX alone. The committee concluded that these estimates were at the lowest end of the range and plausible adjustments in the QALY calculations, for example, in the risk share agreement, or assumptions on quality of life scores for metastatic patients, could potentially increase these estimates substantially.

NICE rejection of Avastin in the NHS will allow Erbitux’s (cetuximab) marketed by Merck KGaA/Eli Lilly/ImClone) to further penetrate the first-line colorectal cancer market in the UK, for which it was approved earlier this year.

Erbitux was recommended by NICE in August 2009 for the treatment of first-line wild type KRAS metastatic CRC patients on the NHS. NICE specified that only patients with unresectable metastatic disease limited to the liver should be eligible for Erbitux treatment, which should not exceed six weeks.

The decision was based on data showing that Erbitux shrinks liver metastases, making them resectable in advanced CRC patients with unmutated KRAS. To date, Avastin treatment has not been shown to significantly improve liver resection rates.

Roche supported its submission with data from pooled analyses of an initial two-arm and a subsequent four-arm study as part of the NO16966 trial.

Avastin was compared in combination with either XELOX or FOLFOX over placebo in combination with XELOX or FOLFOX.

However, the appraisal committee deemed these pooled results ‘inappropriate’ because there was an imbalance of prognostic factors between the arms of the trial.

NICE panel concluded that Avastin in combination with oxaliplatin-containing regimens only gave a modest benefit in terms of effectiveness for first-line metastatic CRC compared with regimens without Avastin.

Avastin, which contains bevacizumab as active ingredient (Genentech/Roche/Chugai) is a humanized monoclonal antibody directed towards vascular endothelial growth factor (VEGF).

VEGF plays an important role in angiogenesis, a key driver of tumor growth. The drug was approved in the US in 2004 and the EU in 2005 for first-line metastatic CRC in combination with 5-fluorouracil-based chemotherapy.

Avastin has gained approval for non-small cell lung cancer, breast cancer, renal cell carcinoma and glioma.

Despite receiving marketing authorization in the UK, Avastin has yet to be recommended for use in the UK’s National Health Service (NHS).

The ability to select patients according to KRAS mutation status influenced the positive NICE recommendation for Erbitux.

Merck KGaA will offer a GBP300 companion diagnostic test with Erbitux that will generate significant savings as it will screen out nearly 40% of CRC patients with the mutated form of KRAS, known to be unresponsive to the agent.

NICE’s negative decision on Avastin will give Merck’s Erbitux the opportunity to become the standard targeted therapy of choice in these specific metastatic colorectal cancer patients.

Moreover, other healthcare systems in the seven major markets are likely to follow the example of NICE by demanding better cost-effectiveness from this expensive class of drugs.

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