Oct 15, 2026
Encorafenib for colorectal cancer: multi-comparator study yields indication of considerable added benefit
If the standard of care in the comparator arm is not the same for all patients, studies often fail to reflect this. The example of encorafenib in metastatic colorectal cancer demonstrates that such studies are feasible.
If the standard of care in the comparator arm is not the same for all patients, studies often fail to reflect this. However, with the BREAKWATER study, the manufacturer has demonstrated that it is indeed possible to individualise treatment in the comparator arm. This is also beneficial for patients. And it can serve as a good example for other manufacturers.
The drug encorafenib is used to treat several types of cancer involving a specific mutation, including colorectal cancer. In an early benefit assessment, the Institute for Quality and Efficiency in Health Care (IQWiG) has now investigated whether encorafenib in combination with the drugs cetuximab and chemotherapy (FOLFOX) offers advantages over the current standard of care in the first-line treatment of adult patients with metastatic colorectal cancer. In this situation, the choice of standard treatment depends on individual circumstances, a factor which the Joint Federal Committee ( GBA) has taken into account in its specification for the comparator therapy.
The multi-comparator study called BREAKWATER was relevant to the IQWiG assessment. In this context, a multicomparator design means that patients in the control group, who received the current standard of care, had several options available to them, thus allowing for individual choice. The BREAKWATER study involved six different chemotherapy regimens of varying intensity, all of which were used in the study. For Katrin Nink, Head of the Oncology Unit within IQWiG’s Drug Assessment Department, this is an extremely positive example: “In our assessments, we often face the problem that manufacturers do not provide us with suitable data when the comparator therapy requires an individualised choice from several options. However, with the BREAKWATER study, the manufacturer has demonstrated that it is indeed possible to individualise treatment in the comparator arm. This is also beneficial for patients. And it can serve as a good example for other manufacturers."
Overall, the study demonstrates considerable added benefit of encorafenib compared with the treatment options available to date, particularly due to significantly prolonged overall survival.
GBA 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 GBA. After publication of the dossier assessment, the GBA conducts a commenting procedure and makes a decision on the extent of the added benefit.