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Lack of robust evidence means NICE unable to approve ovarian cancer treatment in draft guidance

In preliminary draft guidance published today (18 June), a new treatment for ovarian cancer is not recommended for NHS use because the manufacturer did not submit sufficient evidence that the drug benefits patients more than the most widely-used NHS treatments.

The National Institute for Health and Clinical Excellence (NICE) is appraising trabectedin (Yondelis, PharmaMar) in combination with pegylated liposomal doxorubicin (PLDH) for the treatment of relapsed ovarian cancer that is sensitive to platinum-based therapies.

NICE’s independent advisory committee concluded that the evidence submitted by the manufacturer was not robust because it did not compare trabectedin against a current ‘gold-standard’ treatment for relapsed ovarian cancer: paclitaxel in combination with platinum-based chemotherapy. The committee could, therefore, not confirm whether or not the drug extends patients’ lives for longer than one of the more effective and commonly-used treatments for this form of cancer.

This draft guidance has now been issued for consultation: NICE has not yet published final guidance to the NHS.

Sir Andrew Dillon, NICE Chief Executive, said: “In current clinical practice, paclitaxel in combination with platinum-based chemotherapy is widely regarded as one of the most effective treatments for women with platinum-sensitive, relapsed ovarian cancer.

“Unfortunately, the manufacturer did not provide any evidence directly comparing trabectedin with this combination of drugs. The studies that were submitted as evidence compared trabectedin with less commonly-used treatments. The evidence did, however, show that trabectedin is associated with high rates of toxicity on the body’s blood system compared with other, currently available drugs. It was these factors and not necessarily the cost of the treatment that concerned the committee most.”

Sir Andrew Dillon added: “It’s important to remember that not everyone whose cancer has relapsed would be suitable for trabectedin. A range of treatment options do already exist for ovarian cancer and especially fortumours that have returned. In 2005, NICE approved a number of drugs shown to be effective in treating relapsed disease, including paclitaxel in combination with platinum-based chemotherapy, which is now one of the most widely used treatments in clinical practice.”

NICE’s preliminary guidance is now available for public consultation until 9 July 2010. Comments can be made via the NICE website; www.nice.org.uk. Any feedback received during this consultation will be considered by the committee and, following this meeting, the next version of draft guidance will be issued.

Final guidance for trabectedin for relapsed, platinum-sensitive ovarian cancer is expected to be published later this year. Until then, NHS bodies should make decisions locally on the funding of specific treatments.

Notes to Editors

• According to the draft guidance, trabectedin in combination with pegylated liposomal doxorubicin hydrochloride (PLDH) is not recommended for the treatment of women with relapsed platinum-sensitive ovarian cancer.
• The guidance is available to view at: http://guidance.nice.org.uk/TA/Wave19/47 (from Friday 18 June 2010).
• The manufacturer’s submission presented evidence on the clinical effectiveness of trabectedin plus PLDH compared with PLDH, paclitaxel and topotecan as monotherapy.
• The manufacturer estimated that the cost of treatment with trabectedin plus PLDH, assuming an average of six cycles and a body surface area of 1.72 m², is £23,917, excluding administration costs.
• Trabectedin is an intravenous drug that works by damaging the DNA in cancer cells, making the cells unable to grow and spread. It is administered via a drip every three weeks with the recommended dose being 1.1mg per m² of body surface area.
• Ovarian cancer is the fifth most common cancer in women in the UK1 with nearly 6,600 women diagnosed with the disease each year2. It is thought the cancer returns after initial treatment in around 80% of cases and just over two fifths of these patients would be eligible for trabectedin, if the drug were to be approved3.
• Published in 2005, NICE Technology Appraisal No. 91 recommends the following as options for second-line (or subsequent) treatment:
  • paclitaxel in combination with a platinum compound in platinum-sensitive or partially platinum sensitive disease
  • pegylated liposomal doxorubicin hydrochloride in partially platinum-resistant disease
  • single agent paclitaxel or pegylated liposomal doxorubicin hydrochloride in platinum-resistant or platinum refractory disease or for those with an allergy to platinum-based compounds
  • topotecan only where the other recommended options are considered inappropriate.
• Earlier this year, NICE recommended trabectedin as a treatment for some patients with an advanced form of a rare type of cancer called soft tissue sarcoma. This guidance is available to view at: http://guidance.nice.org.uk/TA185.

About NICE

• The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.
• NICE produces guidance in three areas of health:
  • public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
  • health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS
  • clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

1 http://www.cancerhelp.org.uk

2 In 2006, the year for which the latest incidence figures are available, 6,596 women were diagnosed with ovarian cancer (sources: Office for National Statistics. Cancer Statistics registrations: Registrations of cancer diagnosed in 2006, England. Series MB1 no.37. 2008, ISD Online. Cancer Incidence, Mortality and Survival data. 2009, Northern Ireland Cancer Registry. Cancer Registrations in Northern Ireland, 2006. 2008, Welsh Cancer Intelligence and Surveillance Unit. Cancer Incidence in Wales. 2009)

3 According to the manufacturer’s submission, the size of the platinum-sensitive population for ovarian cancer is approximately 2,765 people