The Germany Institute for Quality and Efficiency in Health Care (IQWIG) in 2017 studies the advantages and disadvantages of robociclib in combination with an aromatase inhibitor versus the appropriate comparator therapy in patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer.
There was a concentration of the examination at that time on the application as initial endocrine-based therapy in postmenopausal women. The data of the study expressed no statistically significant advantage, but substantial side effects of the new combination that results in the following conclusion: Ribociclib in combination with an aromatase inhibitor provides lesser benefit than the appropriate comparator therapy.
The therapeutic indication of ribociclib, meanwhile, was extended to pre-menopausal or menopausal women. Since there is no restriction in the combination of the drug to an aromatase inhibitor, it can also be combined with fulvestrant. Apart from the initial treatment, the substance can also be applied as subsequent therapy. As a result, the Federal Joint Committee (G-BA) commissioned IQWIG with a new dossier assessment which was to be based on data from the studies MONALEESA-3 and MONALEESA-7.
In the case of some patients, there is an advantage in overall survival on this basis which results in a hint of a minor added benefit in the outcome category 'mortality.'
Stefan Lange, Deputy Director of the Institute, said that this survival advantage is statistically insignificant when the data are analyzed for only one of the research questions. However, they found it to be adequate to subject the data of the two relevant patient groups participating in the MONALEESA-3 study to joint consideration. In addition to that, the significant threshold has been reached.
In the same light, clear disadvantages accompanied this advantage which is the indications of significant harm in the outcome category "adverse events" commonly referred to as side effects: women who had been treated with ribociclib developed severe diseases of the blood and the lymphatic system much more consistently than the study participants in the comparator arm did.
The affected women developed neutropenia which is lack of neutrophilic granulocytes, immune cells essential for the defense against infections. Eventually, these disadvantages are grave enough to outweigh the hint of a survival advantage.
Overall, the Institute arrived at the following conclusion: an added benefit for postmenopausal women is not proven for any of the research questions. For pre-menopausal and menopausal women, however, the manufacturer presented relevant data only for a subgroup of pretreated women. For these women, lesser benefit in comparison with the appropriate comparator therapy must still be assumed.
Part of the early assessment is the dossier assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) which the G-BA supervises. After the publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
