Olaparib has recently been approved for the adjuvant, i.e. supportive, treatment of early breast cancer. It is an option for patients with BRCA1/2 mutations who have HER2-negative breast cancer at high risk of recurrence that has already been treated with chemotherapy in addition to surgery. In this setting, olaparib can be used alone or together with anti-hormonal therapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) now examined in an early benefit assessment whether this adjuvant treatment provides an added benefit for patients.

According to the findings, olaparib prolongs overall survival and recurrences are less frequent. However, these advantages are accompanied by side effects, some of which are serious. IQWiG’s overall conclusion is therefore: indication of a minor added benefit in comparison with the appropriate comparator therapy, i.e. watchful waiting.

Adjuvant therapy prolongs life and prevents recurrence

Almost exclusively women with early breast cancer and only a few men participated in the studies used for the benefit assessment. During the median observation period of about 40 months, about 8 per cent of patients died in the olaparib group. Of the patients in the comparator group, who received placebo, about 12 per cent died. Recurrences were also less frequent under adjuvant olaparib treatment: With olaparib, 15 per cent of the patients had recurrences, compared with 23 per cent in the comparator group.

“It is rather unusual that an early benefit assessment of an adjuvant therapy shows a difference in terms of both recurrence and overall survival. This corresponds in each case to an indication of considerable added benefit," says Volker Vervölgyi, Division Head in IQWiG’s Drug Assessment Department. “In many other benefit assessments, informative data for overall survival are lacking."

Side effects lead to a downgrading of the added benefit

For other outcomes, negative effects predominate, however. Thus, a number of side effects, in some cases to a major extent, occurred under olaparib, including fatigue, gastrointestinal disorders and anaemia. In addition, side effects were only recorded during treatment and for 30 days afterwards, and not until the end of the study. Other outcomes such as health-related quality of life were also not observed until the end of the study.

Due to the adverse effects described, IQWiG downgraded the extent of added benefit. In summary, there is therefore an indication of a minor added benefit of olaparib in comparison with the appropriate comparator therapy “watchful waiting”.

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 Federal Joint Committee (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