Tebentafusp improves overall survival in patients with untreated metastatic uveal melanoma: NEJM

UK: According to a new study, tebentafusp treatment resulted in longer overall survival than control therapy in previously untreated individuals with metastatic uveal melanoma.

Uveal melanoma is different from cutaneous melanoma in that it has a modest tumor mutational load and a 1-year overall survival rate of around 50% in individuals with metastatic uveal melanoma. Tebentafusp is a bispecific protein that consists of an affinity-enhanced T-cell receptor linked to an anti-CD3 effector capable of redirecting T cells to glycoprotein 100–positive cells. The objective of this study was to check the overall effect of tebentafusp on uveal melanoma.

The findings of this study were published in The New England Journal of Medicine on 23rd September 2021 and this study was undertaken by the team lead by Dr. Paul Nathan.

In this open-label, phase 3 trial, previously untreated HLA-A*02:01–positive patients with metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified by lactate dehydrogenase. Overall survival was the major end goal.

The study outcomes are presented as follows: in the intention-to-treat population, overall survival at one year was 73% in the tebentafusp group and 59% in the control group. The tebentafusp group also had a considerably better progression-free survival rate than the control group. In the tebentafusp group, the most frequent treatment-related adverse events were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100–positive melanocytes), including rash, pyrexia, and itching. After the first three or four doses, the frequency and severity of these side effects were reduced, and the trial therapy was seldom discontinued. There were no documented treatment-related fatalities.

In conclusion, from the data of this study, It was ascertained that tebentafusp has a better outcome and prognosis in uveal melanoma and can be employed by clinicians in the future as a regular practice.

Source: 

Nathan, P., Hassel, J. C., Rutkowski, P., Baurain, J.-F., Butler, M. O., Schlaak, M., Sullivan, R. J., Ochsenreither, S., Dummer, R., Kirkwood, J. M., Joshua, A. M., Sacco, J. J., Shoushtari, A. N., Orloff, M., Piulats, J. M., Milhem, M., Salama, A. K. S., Curti, B., Demidov, L., … Piperno-Neumann, S. (2021). Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. New England Journal of Medicine, 385(13), 1196–1206. https://doi.org/10.1056/nejmoa2103485