Nivolumab (trade name: Opdivo) has been approved since June 2015 for adults with advanced melanoma. The German Institute for Quality and Efficiency in Health Care (IQWiG) had examined its added benefit in a dossier assessment completed in October 2015.
In an addendum, the Institute now assessed study data subsequently submitted by the drug manufacturer in the commenting procedure. In treatment-naive patients whose tumour is BRAF V600 mutation-negative, IQWiG still sees a hint of an added benefit in comparison with the appropriate comparator therapy for women, and an indication of an added benefit for men. The extent of the added benefit increased, however: from "minor" to "considerable" in women, and from "considerable" to "major" in men.
Additional analyses on side effects
The dossier had already shown that treatment-naive patients whose tumour is BRAF V600 mutation-negative have an advantage, which varies by sex. The dossier also contained data on side effects. However, no conclusive interpretation of them was possible because adverse events that constitute progression of the underlying disease were also recorded here.
The drug manufacturer now subsequently submitted adequate analyses on side effects in the commenting procedure. These showed an advantage of nivolumab in comparison with dacarbazine regarding severe and serious adverse events as well as study discontinuation due to adverse events. IQWiG therefore now saw a hint of lesser harm here, the extent of which the researchers rated as minor.
Balancing of benefit and harm now possible
Due to the documents subsequently submitted it was now possible to balance benefit (overall survival) and harm (side effects). Overall, the data showed a hint of a considerable added benefit in female melanoma patients with BRAF V600 mutation-negative tumour, and an indication of a major added benefit in male patients. Evaluable data on symptoms and complications (morbidity) as well as on health-related quality of life are still lacking, however.
The result of the dossier assessment for patients with BRAF V600 mutation-positive tumour is still valid: Since also the data subsequently submitted are unsuitable for the assessment, there is still no hint of an added benefit.
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 manufacturer's dossier and the IQWiG dossier assessment, the manufacturer submitted additional information in the commenting procedure. The G-BA subsequently commissioned IQWiG to assess the data subsequently submitted. IQWiG now presents this assessment in the form of an addendum. The G-BA makes a final decision on the extent of added benefit.