The approval of pertuzumab in free and fixed combination with trastuzumab includes the adjuvant (supportive) therapy of patients with HER2-positive early breast cancer at high risk of recurrence. The German Institute for Quality and Efficiency in Health Care (IQWiG) had already investigated this supportive therapy for the above-mentioned patient group as part of previous early benefit assessments. It had then concluded that an added benefit was not proven in either case. However, the Federal Joint Committee (G-BA) had limited its resulting assessment because further data relevant to the assessment of the drug were expected.

These time limits have now expired and IQWiG has reassessed the benefit of the treatment. The result: The new data suggest a minor added benefit of the adjuvant treatment.

Adjuvant treatment options for early breast cancer

Early breast cancer is when the cancer is limited to the breast, and the lymph nodes in the armpits are hardly affected or not at all. Treatment of this disease is curative in intent – many patients still have a long life ahead of them.

Pertuzumab is a monoclonal antibody. Both pertuzumab in free combination with trastuzumab and the pertuzumab/trastuzumab fixed dose combination are approved for several therapeutic indications and are always combined with chemotherapy. The present dossier assessments relate exclusively to the adjuvant treatment of adult patients with HER2-positive early breast cancer at high risk of recurrence, in combination with chemotherapy. A high risk of recurrence is assumed for node-positive or hormone receptor-negative disease.

The G-BA specified treatment with trastuzumab and a taxane (paclitaxel or docetaxel) as appropriate comparator therapy. Additional administration of an anthracycline (doxorubicin or epirubicin) is possible.

Added benefit for recurrence and overall survival

The benefit assessments used the APHINITY study, which had already been the basis of previous assessments, but now provides data for a longer observation period. Most of the just over 4800 participants in the study were women, and only very few men participated. All patients had undergone surgery to remove their primary tumour before the start of the study. The results of just over 3600 patients at high risk of recurrence are relevant to the benefit assessment.

For these patients, there is now a hint of minor added benefit for overall survival. For recurrences (relapses), the study provides an indication of considerable added benefit. On the other hand, there are indications of negative effects, such as diarrhoea occurring during treatment, but also, for example, serious cardiac failure persisting after treatment.

The treatment is particularly burdensome for patients who are 65 years or older. For example, they are more likely to experience nausea, vomiting and loss of appetite, as well as lower health-related quality of life. In the first assessment, this had led to an overall hint of lesser benefit for this age group.

Longer observation period provides interesting new findings

In the overall view, the positive effects now predominate for all age groups, especially due to fewer recurrences and longer survival: There is an indication of minor added benefit of pertuzumab and pertuzumab/trastuzumab in comparison with the appropriate comparator therapy for patients with HER2-positive early breast cancer at high risk of recurrence.

“The results show how useful it is to limit the period of validity of the resolution on a benefit assessment for certain therapeutic indications," says Volker Vervölgyi, Division Head in IQWiG’s Drug Assessment Department. “The reason is that the observation periods in studies may be too short at the time of the approval and of the early benefit assessment to allow a conclusive assessment of the benefit a treatment has for overall survival," he concludes.

G‑BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G‑BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.

You can find an overview of the results of IQWiG’s benefit assessment in an English extract. In addition, the website informedhealth.org published by IQWiG provides easily understandable information on this benefit assessment.

Source: Institute for Quality and Efficiency in Health Care