Tebentafusp for uveal melanoma: indication of considerable added benefit:

Tebentafusp is a drug for the treatment of a rare disease, uveal melanoma. This malignant tumour disease originates in the eye, but can spread to other organs. After the turnover of the drug with the statutory health insurance exceeded an amount of 30 million euros in the previous 12 calendar months, the manufacturer has now submitted a dossier on the added benefit versus the appropriate comparator therapy.

In its dossier assessment, the Institute for Quality and Efficiency in Health Care (IQWiG) investigated whether the drug offers HLA-A*02:01-positive adults with inoperable or metastatic uveal melanoma an added benefit compared with treatment of physician's choice. Conclusion: The advantages, particularly in the outcome of overall survival, clearly outweigh the disadvantages. There is an indication of considerable added benefit of tebentafusp in comparison with the appropriate comparator therapy.

Open-label RCT with the option of switching to the tebentafusp arm

The manufacturer submitted data from an unblinded randomized controlled trial (RCT) in which only patients with inoperable, metastatic uveal melanoma who had not yet received systemic therapy in the metastatic or advanced stage participated. They were randomly assigned in a 2:1 ratio to treatment with tebentafusp or to treatment of physician's choice. For the vast majority of patients in the control arm, treatment of physician’s choice was pembrolizumab, followed by ipilimumab and dacarbazine.

After the first of two data cut-offs, patients in the control arm had the option to receive follow-up therapy with tebentafusp; around one fifth of them chose up this option. This resulted in a high risk of bias, so that at most hints can be derived from the study - with the exception of the outcomes of overall survival and skin reactions, where the first data cut-off already provided a clear picture.

Advantage in overall survival clearly outweighs the disadvantages

In the patient-relevant outcome of overall survival, the early data yielded an indication of an added benefit, which was still identifiable in the later data cut-off. In addition, one side effects outcome showed a hint of lesser harm than under the comparator therapy.

These positive effects are offset by several hints and one indication of greater harm from tebentafusp in several other outcomes of the side effects category, including severe skin reactions.

Unfortunately, there are no evaluable data for the outcome categories of morbidity and health-related quality of life.

"We weighed up these positive and negative aspects against each other: The survival advantage clearly outweighs the disadvantages," says Volker Vervölgyi, Division Head in IQWiG’s Drug Assessment Department. All in all, there was an indication of a considerable added benefit of tebentafusp compared to treatment of physician's choice. "Fortunately, an informative RCT is available for the assessment of this rare disease that shows that patients in the therapeutic indication benefit significantly from tebentafusp."

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 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.