NICE announced on 25 March 2014 that it is not recommending ZALTRAP® (aflibercept) to the NHS in England and Wales for the treatment of advanced, metastatic colorectal cancer (mCRC).1 Based on the same basic evidence, aflibercept was approved for use in Scotland on 10 March.2
Dr Rob Glynne-Jones, Consultant Clinical Oncologist, Macmillan Lead Clinician in Gastro-Intestinal Cancer, Northwood commented:
"This is another example of NICE failing cancer patients who are in dire need of innovative medicines. With the future of the CDF uncertain, UK cancer patients will continue to die prematurely if the system remains unchanged. Zaltrap is a novel agent which has produced results that extend life in the later stages of colorectal cancer. It is therefore extremely disappointing that NICE has closed the door on this treatment, particularly when you consider that patients with advanced colorectal cancer have very few options."
Steve Oldfield, Sanofi's Managing Director UK and Ireland commented:
"We are extremely disappointed NICE has not approved aflibercept, particularly given that based on the same basic evidence, the Scottish Medicines Consortium accepted aflibercept. Sanofi wanted NICE to be able to approve aflibercept for patients in England and Wales and offered a patient access scheme as part of the appraisal. "
There is significant clinical demand for aflibercept - since the inclusion of aflibercept on the Cancer Drugs Fund (CDF) in England in May 2013, there have been 321 requests for its use, making it the seventh most requested drug on the CDF within its licensed indication.3 However, funding of drugs on the CDF is not guaranteed and the fund itself is planned to terminate in 2016. Furthermore, the CDF does not apply to Wales and Northern Ireland.
Steve Oldfield added: "The lack of a long-term solution for access to innovative cancer medicines is seriously undermining the UK's ability to maintain its status as a world leader in innovative medical technology. More importantly, it risks cancer patients in England and Wales being unable to access effective new medicines. NICE issued no positive final guidance for cancer medicines in 2013 - it's clear that something needs to change.
Colorectal cancer is the second most common cause of cancer death in the UK.4 In its advanced stages it can become difficult to treat and until now there have been limited treatment options available.5
Aflibercept was approved by the European Commission in February 2013 for use in combination with irinotecan/ 5-fluorouracil/ folinic acid (FOLFIRI) chemotherapy for the treatment of adults with mCRC that is resistant to or has progressed after an oxaliplatin-containing regimen.6 Aflibercept is proven to significantly improve overall survival (OS), progression free survival (PFS) and overall tumour response rate versus placebo plus FOLFIRI chemotherapy in patients with mCRC whose disease has progressed after an oxaliplatin-based regimen.7
As the first multiple anti-angiogenic agent of its kind, aflibercept has a novel mode of action that works in a different way to other available treatments8 licensed for use in the UK. Aflibercept works by preventing the formation of new blood vessels within and around a tumour,7 thereby stopping or slowing the spread of cancer.
The VELOUR trial is the only double-blind, randomised study to have demonstrated a statistically significant and clinically meaningful benefit in overall survival, progression free survival and response rate, in combination with FOLFIRI in this setting.7
The Cancer Drugs Fund (CDF)
In order to improve access to new cancer drugs, the Cancer Drugs Fund (CDF) was established in 2010. It provides an additional £200m each year to enable patients with cancer in England to receive access to drugs that are either not routinely available on the NHS or have not been approved or appraised by NICE. Aflibercept is listed on the Cancer Drugs Fund.
NICE's appraisal of aflibercept:
NICE's final negative guidance comes following an Appeal by Sanofi. The basis of the Appeal was that the NICE Committee did not apply special criteria introduced for drugs used at the end of life, despite published data demonstrating that aflibercept does meet these criteria.
In 2009, NICE agreed new criteria for appraising drugs that can extend life for people with advanced cancer. Up to 28 February 2014, NICE had reviewed 46 medicines under these criteria, of which only 12 resulted in positive recommendations for use in the NHS.9 Bowel cancer patients have fared particularly badly, with NICE issuing 'not recommended' guidance for the four most recently appraised medicines suitable for this patient group.1,10 This is set against a backdrop of cancer outcomes in the UK remaining the worst against comparator nations,11 despite the introduction of government reforms.
Upcoming changes to the NICE appraisal process
NICE is set to announce draft proposals for changes to its appraisal criteria to introduce a system of "value-based assessment". However, there have been a number of concerns raised that this new system may not improve access to drugs and could be discriminatory against older patients.