The top story for melanoma 2021 is the overall survival benefit of tebentafusp for uveal melanoma.
Uveal melanoma is an orphan disease since it should be considered a rare cancer because it is distinctly different from “regular” cutaneous melanoma. It is genetically completely different in terms of other driver mutations (GNAQ and GNA11) being found in uveal melanoma. Also, the tumor mutational burden is much lower, and it has been suggested therefore that it has a much lower response to immune checkpoint blockade. Finally, the clinical course of the disease is different, with metastases only occurring after a long period, often confined to the liver.
Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100–positive cells.
The phase III randomized controlled trial “Overall Survival Benefit With Tebentafusp in Metastatic Uveal Melanoma”1 was able to show an overall survival benefit for this novel drug over investigator’s choice of therapy (in many cases, immune checkpoint blockade). Thereby, the result of this study is practice-changing for this orphan disease and rare cancer, and that alone is already quite unique because improvements for such niches are very difficult to achieve.