Talazoparib in breast cancer: hint of considerable added benefit
Advantages in health-related quality of life, symptoms and side effects outweigh disadvantages
Talazoparib is another drug from the substance class of PARP inhibitors, which also includes olaparib and rucaparib, for example, to have been approved this year for the treatment of breast cancer. Prerequisites for its use are the presence of so-called germline BRCA1/2 mutations, HER2-negative, locally advanced or metastatic breast cancer and pretreatment with an anthracycline and/or a taxane in the neoadjuvant, adjuvant, locally advanced or metastatic setting – if suitable for the patients. Besides, patients with hormone receptor-positive breast cancer should have been treated with a prior endocrine-based therapy, unless this therapy is unsuitable for them.
The German Institute for Quality and Efficiency in Health Care (IQWiG) now examined in an early benefit assessment whether talazoparib offers an added benefit for these patients in comparison with the appropriate comparator therapy (ACT). Its conclusion: There is a hint of considerable added benefit. However, important data about the wellbeing of the patients after progression are missing.
Tumour cells die
PARP inhibitors can be an alternative to chemotherapy for people with locally advanced or metastatic breast cancer and a certain germline mutation. They block poly ADP-ribose polymerase (PARP for short), enzymes for DNA repair. If the breast cancer associated genes 1/2 (BRCA1/2 for short) are also mutated, it is no longer possible for the cells to repair single-strand breaks in their DNA. Since this kind of DNA damage in tumour cells occurs frequently after treatment with cytostatics such as a chemotherapeutic agent, a taxane or an anthracycline, many tumour cells die as a result. Thus, a corresponding pretreatment and determination of the germline mutation status are prerequisites for the use of a PARP inhibitor because the cancer cells can avoid the PARP blockade if the BRCA1/2 gene is not mutated.
Assessment on the basis of a subpopulation of a multi-comparator study
The ACT specified by the Federal Joint Committee (G-BA) was chemotherapy with capecitabine, eribulin or vinorelbine, or anthracycline- or taxane-containing therapy, provided the latter is still an option for the patients. In contrast to other therapies used (e.g. platinum-containing therapies), these drugs are approved in Germany for the present therapeutic indication.
The assessment was conducted on the basis of the multi-comparator study EMBRACA, in which a subpopulation was treated in accordance with the ACT. Since the risk of bias of the study and its outcomes was high, however, no more than hints of greater benefit or harm can be derived from the results.
Observations were discontinued after progression
The assessment was made more difficult by the short observation period, which differed notably between the study arms, for all outcomes except mortality: The last time the patients were asked about their symptoms and quality of life was 30 days after the end of treatment. The median treatment duration was just under seven months in the talazoparib arm, but – due to many premature discontinuations due to progression – only about three months in the chemotherapy arm. Hence, the decrease in the response to the corresponding questionnaires was more pronounced here than in the talazoparib arm.
This data situation does not allow to draw conclusions about the time to definitive deterioration. In particular, there are no data on the patients’ wellbeing after disease progression and on the effects of the progression on their quality of life. “It would be necessary to record these changes over the entire study period, including the time after progression,” says Volker Vervölgyi, Division Head at IQWiG and responsible for the benefit assessment of oncologic drugs. “And this would be feasible, too.”
Positive effects predominate
No statistically significant difference between the treatment groups was shown for the outcome “overall survival”. In the other outcome categories, however, there were many positive and only few negative effects of talazoparib in comparison with the ACT. For example, health-related quality of life – both global health-related quality of life and in all relevant functional scales – was better than in the comparator arms of the study; the extent was mostly “considerable”. Advantages in several symptom scales, such as pain or insomnia, were also shown in non-serious and non-severe symptoms or late complications, outcomes of the category of morbidity. In serious/severe side effects, besides the positive effects, there were also negative effects of talazoparib in comparison with the ACT. The disadvantages were limited to the specific side effects “anaemia” and “thrombocytopenia”. In the category of non-serious or non-severe side effects, on the other hand, the new drug had advantages in several outcomes.
In the overall consideration, there is a hint of considerable added benefit of talazoparib in comparison with the ACT.
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.
More English-language information will be available soon (Sections 2.1 to 2.5 of the dossier assessment as well as easily understandable information on informedhealth.org). If you would like to be informed when these documents are available, please send an e-mail to email@example.com.