A treatment for an aggressive form of non-Hodgkin's lymphoma is not recommended for NHS use in draft guidance by the National Institute for Health and Care Excellence (NICE). The recommendation, published for public consultation, comes after an independent committee of experts concluded there was insufficient evidence to show that pixantrone (Pixuvri, Cell Therapeutics) is more effective than current NHS treatments and it does not represent good value for money for the health service.

Pixantrone has a conditional licence to treat adults with aggressive non-Hodgkin B-cell lymphoma (NHL) that has either returned after treatment (relapsed) or become resistant to current therapy (refractory) multiple times and who have received at least two previous types of treatment. NICE is developing guidance for the NHS on the use of pixantrone for this specific group of people.

Sir Andrew Dillon, NICE Chief Executive, said: "For NICE to recommend a treatment, it must be shown to work at least as well as currently available NHS treatments taking into consideration any side effects that particular treatment might cause and also its cost to the NHS. Unfortunately in this case, the clinical trial evidence submitted to the Appraisal Committee highlighted a number of uncertainties that called into question the true benefit people might receive from this treatment."

Non-Hodgkin B-cell lymphoma is a cancer of the lymphatic system, which forms part of the body's immune system, and affects the body's B-cells (white blood cells found in bone marrow). Standard NHS treatment includes the drug rituximab (MabThera) as well as chemotherapy.

Consultees, including the manufacturer, healthcare professionals and members of the public are now able to comment on the preliminary recommendations which are available to view on the NICE website. The consultation is open until Wednesday 1 May 2013 and any comments received will be fully considered by the Committee during the next stage of guidance development.

Until final guidance is issued to the NHS, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations across the country.

Ends

Notes to Editors

About the guidance

1. The draft guidance will be available on the NICE website from Thursday 11 April 2013.

2. Pixantrone has a conditional UK marketing authorisation ‘as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphomas (NHL). The benefit of pixantrone treatment has not been established in patients when used as fifth line or greater chemotherapy in patients who are refractory to last therapy'. This means it is conditionally approved for patients who have received at least two previous lines of treatment. This conditional marketing authorisation is linked to results being provided from a phase III clinical trial (PIX306), which is investigating pixantrone plus rituximab versus gemcitabine plusrituximab in patients with relapsed or refractory aggressive non-Hodgkin B-cell lymphoma who have previously received a rituximab-containing regimen.

3. When developing the preliminary recommendations, the independent Appraisal Committee considered data from the PIX031 clinical trial submitted by the manufacturer and heard evidence from clinical experts and patient representatives. The committee noted a number of uncertainties associated with the clinical trial including that it had failed to recruit the planned number of patients and that its primary endpoint was complete or unconfirmed complete response to treatment rather than a primary end point of overall survival or progression-free survival which is preferred by European regulators.

4. Clinical experts told the committee that rituximab is an integral part of standard first-line treatment in the NHS and also often used in second-line therapy but only just over half of the trial's participants had previously received rituximab. The committee concluded that differences in previous treatment between the PIX301 trial population and UK clinical practice meant there was considerable uncertainty in determining the clinical effectiveness for a UK population. The Appraisal Committee was also aware of the specific obligation to the European Medicines Agency inpixantrone's UK marketing authorisation, which stipulated that an additional trial was required to confirm the clinical benefit in patients who have previously received rituximab. The committee further concluded that there was considerable doubt over the clinical benefit of pixantrone in patients who had previously received rituximab, and that this applied to virtually all patients with relapsed or refractory aggressive B-cell lymphoma in England and Wales.

5. The Appraisal Committee also noted a lack of statistically significant difference in overall survival between treatment arms in the PIX301 trial as well as the fact that the differences between treatment groups were not always statistically significant. This led the committee to conclude there was insufficient evidence to show that pixantrone is more clinically effective than treatments currently used in clinical practice.

6. The Appraisal Committee agreed that the most plausible Incremental Cost-Effectiveness Ratio (ICER) should be for the comparison of pixantrone with treatment of physician's choice in people who had aggressive B-cell lymphoma confirmed by central independent pathological review and considered that the population should not be restricted to third- or fourth-line treatment, in line with the UK marketing authorisation. The manufacturer estimated that the ICER for this population was £32,700 per QALY gained but the independent Evidence Review Group (ERG) estimated it to be £60,200 per QALY gained. The committee concluded that the most plausible cost-effectiveness estimate, based on available evidence, would lie within the range between these two values. The committee noted that this range was based on data from the PIX301trial, where a sizeable proportion had not previously received rituximab and therefore concluded that the ICER could be much higher for the current UK patient group, where rituximab is given as part of standard first-line care for aggressive non-Hodgkin B-cell lymphoma.

7. Pixantrone is a drug that is administered intravenously. The recommended dosage is 50 mg/m2 on days 1, 8, and 15 of each 28-day cycle for up to six cycles. According to the manufacturer, it costs £553.50 per 20 ml vial (which contains 29 mg free base pixantrone, which is equivalent to 50 mg pixantrone dimaleate). This is excluding VAT. The estimated cost of a course of treatment is £19,926.18 (costs calculated over four cycles using an average of three vials per dose based on the median length of treatment in the PIX301 trial). Costs may vary in different settings because of negotiated discounts.

8. The committee considered that there was insufficient evidence demonstrating that pixantrone offered an extension to life of an additional three months, compared with current NHS treatment and was not persuaded that the estimates of the extension to life were robust. Because of this, the committee concluded that pixantrone did not fulfil the criteria to be considered as a life-extending, end-of-life treatment.

9. Non-Hodgkin's lymphoma is the sixth most common cancer in the UK; in 2010, 12,180 people were diagnosed with the disease[1]. The manufacturer estimates that 1,650 people with aggressive non-Hodgkin B-cell lymphoma would be eligible to receive pixantrone, if it were to be recommended.

10. The Scottish Medicines Consortium (SMC) has not produced any advice for NHS Scotland on the use of pixantrone for people with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphomas (NHL).

About NICE

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