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NICE has yesterday issued draft guidance not recommending pertuzumab (Perjeta, Roche Products) to treat HER2-positive breast cancer because it is uncertain how the responses to treatment seen in the clinical trials translate into long term benefits for patients.

Pertuzumab is licensed for use in combination with trastuzumab (Herceptin) and docetaxel (a type of chemotherapy) before breast cancer surgery to shrink the cancer so that it becomes operable.

The draft guidance looks at pertuzumab used in this way to treat HER2-positive breast cancer that is locally advanced, inflammatory, or early-stage and at high risk of coming back.[i]

The committee concluded that there was a lack of long-term evidence comparing pertuzumab with other treatments used before breast cancer surgery. There was evidence that adding pertuzumab to trastuzumab and docetaxel was more successful at getting rid of cancer in the breast and lymph nodes before surgery but it was very uncertain about the extent to which this would reduce the risk of the disease recurring and result in longer survival..

Over 50,000 women and around 340 men are diagnosed with breast cancer each year in the UK[ii] with about 10-15% of these characterised as HER2-positive breast cancer.

Pertuzumab costs £2,395 per 420 mg vial (excluding VAT). The total cost of treatment with pertuzumab ranges from £7,185 (3 cycles of treatment) to £16,765 (6 cycles of treatment).

Sir Andrew Dillon, NICE chief executive, said: “In order to be able to recommend pertuzumab as an addition to trastuzumab and chemotherapy, the committee needed to have more evidence of its long-term clinical benefits, particularly its impact on overall survival.

“On the basis of the evidence presented, the committee was very unsure about the extent of these benefits.

“Taking all the uncertainties around the clinical effectiveness of pertuzumab into account, as well as uncertainties with the economic data presented by the company, the committee concluded that it could not recommend the drug for the treatment of HER2-positive breast cancer before surgery as a good use of NHS resources.”

Although the NICE draft guidance does not recommend pertuzumab, it does state that people already receiving the drug should continue until they or their doctor thinks it’s appropriate to stop.

Consultees, including the company, healthcare professionals and members of the public are able to comment on the draft recommendations via the NICE websiteuntil Monday 13 June 2016. All comments received during this consultation will be considered by the committee and a second draft of the guidance will then be published.  If there are no objections at that stage, NICE will publish final guidance to the NHS. Until then, NHS bodies should make decisions locally on the funding of specific treatments. 

For more information call the NICE press office on 0300 323 0142 or out of hours on 07775 583 813.

Notes to Editors

About the draft guidance

1. The draft guidance for pertuzumab (with trastuzumab and docetaxel) for the neoadjuvant treatment of HER2-positive, locally advanced, inflammatory or early-stage breast cancer  will be available from the NICE website from Friday 20 May 2016. Embargoed copies are available via https://share.nice.org.uk. To access the shared folder, the username is PressMedia1 – the password will be sent out in a separate email.
2. Pertuzumab is being appraised in combination with trastuzumab and docetaxel as a neoadjuvant treatment for HER2-positive breast cancer that is locally advanced, inflammatory or early stage.
3. In considering the cost effectiveness of pertuzumab the committee noted that there were a number of different base-case scenarios provided by the company (3 base cases ranging from £8,215 to £19,939 per quality-adjusted life year [QALY] gained) and the evidence review group (ERG) (£23,467 per QALY gained), but that all models were subject to similar levels of uncertainty.
4. In exploratory analyses, both the company and ERG found the estimates of cost effectiveness were most sensitive to assumptions about clinical effectiveness. Altering pathological complete response rates for pertuzumab led to incremental cost effectiveness ratios (ICERs) ranging from £841 to £67,157 per QALY gained in the company model (compared with £17,297 per QALY gained in the company’s original base case) and from £5,959 to £76,515 per QALY gained in the ERG exploratory analyses. The committee agreed that the model’s sensitivity to this assumption was particularly concerning because of the uncertainty about the use of pathological complete response as a surrogate for survival outcomes.
5. The committee was also concerned that the uncertainty it had identified in the cost and utility assumptions were likely to increase the ICER. For costs, the company model included a possible overestimation of metastatic treatment costs (because of the inclusion of treatments for metastatic disease that have been available only through the cancer drugs fund [CDF]).
6.  Although the sensitivity of the model to these cost and utility assumptions had not been fully explored, the committee noted that in the ERG’s model, changing the costs of metastatic treatment to the cheapest treatment (rather than using a weighted average) substantially increased the ERG’s base-case ICER by around £10,000 per QALY gained.
7. Overall the committee agreed that there was too much uncertainty to determine a most plausible ICER, but it had identified uncertainties in the cost and utility assumptions that would be likely to increase all base-case ICERs upwards.
8. Final guidance is due in September 2016.

About pertuzumab

1. Pertuzumab (Perjeta, Roche) is a recombinant monoclonal antibody which targets human epidermal growth factor receptor 2 (HER2)-positive breast tumours. It interrupts the activation of the HER2 intracellular signalling pathway, leading to cell growth arrest and apoptosis. It is administered by intravenous infusion.
2. Pertuzumab has a marketing authorisation in the UK ‘in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer at high risk of recurrence’. The recommended dosage of pertuzumab is an initial loading dose of 840 mg, followed by a maintenance dose of 420 mg every 3 weeks for 3 to 6 cycles.
3. Pertuzumab costs £2,395 per 420 mg vial (excluding VAT). Costs may vary in different settings because of negotiated procurement discounts.

References

[i] Breast cancer is described as ‘early’ if it is restricted to the breast, or the breast and nearby lymph nodes, and has not spread to other parts of the body (clinical stages 1 and 2). It is described as ‘locally advanced’ if the cancer is in a large part of the breast (more than 5 cm) but has not spread to other parts of the body (clinical stage 3), and described as ‘advanced’ if it has spread to other parts of the body and cannot be completely removed by surgery (clinical stage 4).

[ii] Inflammatory breast cancer is a rare but aggressive type of breast cancer in which cancer cells grow along, and block the lymph nodes in the skin of the breast causing it to become inflamed and swollen. Inflammatory breast cancer affects the breast differently and usually the whole breast and the overlying skin are affected (clinical stage 3 or 4).

[iii] These figures have been taken from Cancer Research UK’s website and were calculated from data provided by the Office for National Statistics, the Northern Ireland Cancer Registry, Welsh Cancer Intelligence and Surveillance Unit and ISD Scotland. More information can be found at:http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/.

About NICE

The National Institute for Health and Care Excellence (NICE) is the independent body responsible for driving improvement and excellence in the health and social care system. We develop guidance, standards and information on high-quality health and social care. We also advise on ways to promote healthy living and prevent ill health.

Our aim is to help practitioners deliver the best possible care and give people the most effective treatments, which are based on the most up-to-date evidence and provide value for money, in order to reduce inequalities and variation.

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