Uncertainty over clinical benefit means NICE says no to ovarian cancer drug in draft guidance

The National Institute for Health and Care Excellence (NICE) remains unable to recommend trabectedin (Yondelis, PharmaMar) for relapsed ovarian cancer due to continued concerns over how well the drug works compared with the most commonly-used treatments, according to further draft guidance published today (17 September).

This draft guidance is now with consultees who have the opportunity to appeal against the proposed recommendation. NICE has not yet issued final guidance to the NHS.

NICE is currently considering whether trabectedin, in combination with pegylated liposomal doxorubicin (PLDH), should be recommended for NHS use in patients with ovarian cancer that has returned six months or more after initial treatment with chemotherapy that includes platinum (platinum-sensitive disease). According to clinical experts, re-treatment with platinum-based chemotherapy is the preferred option for relapsed platinum-sensitive disease. However, the manufacturer did not submit any evidence comparing trabectedin with this type of treatment but instead compared it with drugs that did not include platinum. In platinum-sensitive disease this type of treatment is usually reserved for patients who cannot have platinum-based drugs for reasons such as having had an allergic reaction to platinum in the past.

Sir Andrew Dillon, NICE Chief Executive, said: “To accurately tell whether a particular treatment would be a good use of NHS resources, the evidence needs to show how well it works compared with the more commonly-used treatments. In the case of relapsed platinum-sensitive ovarian cancer, this would be platinum-based chemotherapy. Unfortunately, the manufacturer did not compare trabectedin with this type of treatment and the data that was submitted as evidence was not considered robust. This means that we cannot be sure that trabectedin extends patients' lives for longer than the most routinely used treatments currently available.”

Although a direct comparison with platinum-based chemotherapy was not submitted as evidence, the Appraisal Committee did look at other research to assess whether trabectedin should be recommended in the NHS. The manufacturer's main evidence compared trabectedin plus pegylated liposomal doxorubicin hydrochloride (PLDH) with PLDH alone in ovarian cancer patients with different levels of platinum sensitivity[1]. Results suggested that the drug was most effective in women with ovarian cancer that recurred between 6 and 12 months after their initial platinum treatment. However, the clinical trial was not designed to look specifically at this group of women and the Committee could not be sure that the effectiveness of trabectedin in this group was genuinely different from that seen in the wider group of patients for which the drug is licensed. Based on the evidence available the committee concluded that the cost of trabectedin was too high relative to the benefits it brings for patients.

This latest draft guidance from NICE has been developed following preliminary draft guidance (in which the drug was not recommended) and a subsequent consultation period earlier this year. It is now subject to appeal by consultees before final guidance is published. Until this happens, NHS bodies should make decisions locally on the funding of specific treatments.


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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: (from Friday 17 September 2010).
  • 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.
  • The independent Appraisal Committee agreed the incremental cost-effectiveness ratio (ICER) based on the evidence available could be higher than £95,000 per QALY gained.
  • 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 UK[2] with nearly 6,600 women diagnosed with the disease each year[3]. It is thought the cancer recurs 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 approved[4].
  • 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:

About NICE

1. The National Institute for Health and Care 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.

2. 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] A patient's level of platinum-sensitivity is indicated by the length of time it takes for their disease to return after initial treatment with platinum-bed therapies - the longer this takes, the greater the patient's level of platinum sensitivity).


[3] 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)

[4] According to the manufacturer's submission, the size of the platinum-sensitive population for ovarian cancer is approximately 2,765 people

This page was last updated: 16 September 2010

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