The antibody-drug conjugate trastuzumab deruxtecan has been approved since January 2021 for pretreated adults with HER2-positive breast cancer that has metastasised or can no longer be operated on.
Breast cancer is called “HER2-positive” when the tumour cells have many HER2-type receptors onto which growth factors dock, stimulating cell division.
The approval was initially granted for patients who have previously received two or more HER2-targeted therapies.
Since July 2022, it can also be used in patients who have previously received one or more HER2-targeted therapies.
In an early benefit assessment from November 2022, the German Institute for Quality and Efficiency in Health Care (IQWiG) had already assessed trastuzumab deruxtecan in patients who have previously received two or more HER2-targeted therapies.
However, with no suitable data available at that time, IQWiG rated the added benefit as not proven.
Already at that time point, the drug manufacturer referred to its ongoing DESTINY-Breast02 study, the results of which were not yet available when the dossier was submitted.
When they did become available during the commenting procedure for the early benefit assessment, the manufacturer submitted the data.
On the basis of this new evidence, the IQWiG addendum to the early benefit assessment of trastuzumab deruxtecan in this therapeutic indication overall now finds a considerable added benefit in comparison with the appropriate comparator therapy.
DESTINY-Breast02 is a randomised controlled trial (RCT) in 608 patients, comparing trastuzumab deruxtecan with treatment of physician’s choice (here: lapatinib in combination with capecitabine or trastuzumab in combination with capecitabine).
The advantage of treatment with trastuzumab deruxtecan is particularly clear for overall survival: Median survival of patients in the intervention group was just over one year longer than in the comparator group (39.2 months versus 26.5 months).
In addition, a relevant advantage in comparison with the comparator group was shown for several aspects of health-related quality of life (physical, cognitive, social and role functioning) – even though these patient-reported outcomes were recorded for a shorter period of time, i.e. up to three months after the end of treatment.
Positive effects were also observed for the patient-reported outcomes of “pain”, “diarrhoea”, “symptoms in arm region”, and for serious side effects.
Regarding specific side effects, there were both positive and negative effects of trastuzumab deruxtecan.
In summary, IQWiG therefore sees considerable added benefit of trastuzumab deruxtecan in comparison with treatment of physician’s choice for adults with unresectable or metastatic HER2-positive breast cancer who have previously received two or more HER2-targeted therapies.
The approval of trastuzumab deruxtecan was initially based on limited data from a single-arm study.
These data presented in the original dossier did not allow to conduct a comparison with existing treatment options.
However, the manufacturer had started the RCT DESTINY-Breast02 as early as September 2018, so that patient recruitment was already completed at the time of approval, and first data could be submitted in the commenting procedure of the early benefit assessment.
“The example of the DESTINY-Breast02 study shows that it is necessary and possible to plan and start the necessary comparative studies even before approval is granted," says Thomas Kaiser, Head of IQWiG’s Drug Assessment Department. “Having completed recruitment for its RCT already before the approval, the manufacturer of trastuzumab deruxtecan was able to subsequently submit informative data only a few weeks after the first IQWiG assessment. This is the only way we can obtain informative evidence for clinical practice even in cases where approval is granted on the basis of very limited data. Other manufacturers should follow this positive example."
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.
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