Loading
10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
A melanoma inside the eye that is biologically unrelated to skin melanoma: different mutations, no response to standard immunotherapy, and a tendency to spread to the liver years later. Tebentafusp is the first drug ever to extend survival in the metastatic disease.
Uveal melanoma arises from melanocytes of the choroid, ciliary body or iris and is driven by GNAQ/GNA11 (or CYSLTR2/PLCB4) mutations activating Gαq signalling, with metastatic risk set by BAP1 loss and monosomy 3 (gene-expression class 2, PRAME expression) versus SF3B1 and EIF1AX mutations (lower risk). The primary tumour is controlled by plaque brachytherapy or proton beam in most cases (COMS showed equivalence to enucleation), but about half of patients relapse, typically in the liver, with a median survival historically under a year.
Unlike cutaneous melanoma, the tumour mutational burden is low and checkpoint inhibitors give response rates around 5%. Tebentafusp, a gp100×CD3 ImmTAC restricted to HLA-A*02:01, was the first therapy to improve overall survival in metastatic uveal melanoma (IMCgp100-202, 2021; approved 2022). Liver-directed therapy (percutaneous hepatic perfusion with melphalan, approved 2023 as Hepzato; radioembolisation; resection) controls hepatic disease. Darovasertib (PKC inhibitor) with crizotinib is in phase 2/3 in metastatic and neoadjuvant settings.
| Setting | Approach | Guideline |
|---|---|---|
| Primary tumour | Plaque brachytherapy (I-125 or Ru-106) or proton beam radiotherapy for most; enucleation for large tumours; prognostic biopsy for GEP/chromosome 3. | NCCN Category 2A |
| Surveillance | Risk-adapted liver imaging (MRI/ultrasound) every 6-12 months for high-risk GEP class 2 / monosomy 3; no proven adjuvant therapy. | not mapped |
| Metastatic, HLA-A*02:01-positive | Tebentafusp weekly (OS 21.7 vs 16.0 months vs investigator's choice); manage cytokine release and rash. | NCCN Category 1, ESMO-MCBS 4 |
| Metastatic, HLA-A*02:01-negative or liver-dominant | Percutaneous hepatic perfusion with melphalan (FOCUS trial; approved 2023), radioembolisation, hepatic resection; ipilimumab-nivolumab (~15% response); clinical trials (darovasertib-crizotinib). | not mapped |