UK NICE Rejects 3 Drugs for Metastatic Colorectal Cancer

Zosia Chustecka

September 06, 2011

September 6, 2011 — Three targeted therapies — bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix, Amgen) — have been rejected in the United Kingdom for use in patients with metastatic colorectal cancer that has progressed after first-line therapy.

The recommendation against the use of these drugs comes in a provisional guidance issued by the National Institute for Clinical Excellence (NICE).

Comments are now invited, and the committee is open to hearing from manufacturers about patient access schemes. If this provisional guidance is finalized, use of these 3 targeted drugs in this clinical scenario will not be covered by the National Health Service (NHS), which means that the only way that patients can gain access to these treatments is by paying privately.

The high cost of all 3 targeted therapies is obviously an issue.

We have to be confident that the benefits justify the cost of the drugs.

Noting that the NHS already covers 6 drugs for use in colorectal cancer, NICE chief executive Andrew Dillon explained that "we are disappointed not to be able to recommend cetuximab, bevacizumab, and panitumumab at this stage, but we have to be confident that the benefits justify the cost of the drugs."

He further noted that the independent appraisal committee that reviewed the clinical data "does not feel that it has enough clear evidence, especially in the case of bevacizumab, to be able to recommend these drugs for use on the NHS."

Current guidance recommends 5-fluorouracil plus folinic acid in combination with oxaliplatin (FOLROX) or irinotecan (FOLFORI) as a first-line treatment option.

Alternative first-line options recommended for metastatic colorectal cancer are the oral analogues 5-fluorouracil, capecitabine, and tegafur, used in combination with uracil (and folinic acid)

For subsequent therapy in advanced colorectal cancer, NICE recommends the use of FOLFOX or irinotecan alone.

The current recommendations also allow use of cetuximab — 1 of the 3 targeted therapies rejected in the latest provisional guidance — but only in a highly specific patient population. The current recommendation allows the use of cetuximab in patients "with a certain genetic profile whose metastatic disease is limited to liver with the aim to make the metastases operable."

In this latest appraisal, cetuximab was considered for second-line use in metastatic colorectal cancer that has progressed after first-line chemotherapy. In this situation, NICE found "uncertainties" when it looked at overall survival for cetuximab plus irinotecan, based on the mixed-treatment comparison, although the committee did acknowledge that cetuximab plus best supportive care prolonged life in the third-line or later setting, relative to best supportive care alone.

However, the estimated cost for both of these scenarios was unacceptably high. NICE uses a threshold of around £30,000 for cost effectiveness.

The addition of cetuximab to best supportive care would increase costs to an estimated £90,000 per quality-adjusted life-year (QALY) gained; the addition of cetuximab plus irinotecan to best supportive care would cost £88,000 per QALY gained.

The same appraisal — for the same patient population with [if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:Compatibility> <w:BreakWrappedTables /> <w:SnapToGridInCell /> <w:WrapTextWithPunct /> <w:UseAsianBreakRules /> </w:Compatibility> <w:BrowserLevel>MicrosoftInternetExplorer4</w:BrowserLevel> </w:WordDocument> </xml><![endif][if gte mso 10]> <style> /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman";} </style> <![endif]metastatic colorectal cancer that has progressed after first-line chemotherapy — also found "uncertainties" in the evidence for the other 2 targeted therapies.

In the case of panitumumab, the committee questioned the magnitude of survival benefit, compared with best supportive care. It also estimated that the cost of adding panitumumab to best supportive care would fall in the region of £110,000 to £150,000 per QALY gained.

For bevacizumab, the committee found "no evidence to show by how long" overall survival was extended when this drug was combined with a nonoxaliplatin chemotherapy as a second- or third-line treatment for metastatic colorectal cancer in patients who did not respond to first- or second-line chemotherapy. Because of this lack of evidence, the committee said it was unable to estimate cost effectiveness. In addition, the committee noted that it was told by the manufacturer (Roche) that the company had not submitted an economic model "because it did not believe it would be possible to establish that bevacizumab is cost effective as a second-line treatment for metastatic colorectal cancer."

For an American view on this latest news, Medscape Medical News approached colorectal cancer expert John Marshall, MD, professor of medicine and chief of hematology/oncology at Georgetown University, Washington, DC, who posts the Marshall on Oncology videoblog.

"One perspective of these decisions by NICE is that they are restricting the British people from access to life-extending drugs," Dr Marshall noted. "Another is that these drugs are not curative and only extend survival by a few months on average, and are therefore not worth the high price tag," he continued. "Essentially, there is not enough money to go around and they have to make these hard decisions."

Referring to his colleagues in the United States, Dr Marshall added: "While we look down on the British for this decision, we have to realize that we in the United States are about to go through the same exact process and will have to make hard decisions. What we all are seeking is a measure of value that we can all agree on."

"The Ruesch Center for the Cure of Gastrointestinal Cancers is hosting a symposium in Washington, DC, on December 1 and 2, entitled Defining Value in Cancer Care. It is designed to help us focus our own value decisions in the United States. We will be examining the decision processes in place in Great Britain and Canada to help inform us as we go forward," he noted.


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