Uveal melanoma
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.
State of the art today
- Liver-directed therapy has a randomised trial (FOCUS) behind percutaneous hepatic perfusion.
- Gene-expression profiling reliably separates patients who will and will not metastasise, but there is still no adjuvant therapy that helps them.
- Gαq-pathway inhibition (darovasertib ± crizotinib) is the leading targeted strategy.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Tebentafusp is the first TCR-based bispecific approved in any cancer and the first drug to improve survival in metastatic uveal melanoma.
About 5-7 per million per year (the most common primary eye cancer in adults); half of patients eventually develop metastases, almost always in the liver.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Plaque brachytherapy (I-125 or Ru-106) or proton beam radiotherapy for most; enucleation for large tumours; prognostic biopsy for GEP/chromosome 3.
Risk-adapted liver imaging (MRI/ultrasound) every 6-12 months for high-risk GEP class 2 / monosomy 3; no proven adjuvant therapy.
Tebentafusp weekly (OS 21.7 vs 16.0 months vs investigator's choice); manage cytokine release and rash.
Percutaneous hepatic perfusion with melphalan (FOCUS trial; approved 2023), radioembolisation, hepatic resection; ipilimumab-nivolumab (~15% response); clinical trials (darovasertib-crizotinib).
Subtypes & biomarkers
top- Choroidal melanoma (~90%)
- Ciliary body melanoma
- Iris melanoma (best prognosis)
- GEP class 1A/1B (low risk) vs class 2 (high risk)
- BAP1-mutant / monosomy 3 (high metastatic risk)
- GNAQ / GNA11 mutations
- BAP1 loss and monosomy 3
- SF3B1, EIF1AX (lower risk)
- Gene-expression profile (DecisionDx-UM class 1/2) and PRAME
- HLA-A*02 :01 (tebentafusp eligibility)
- Liver MRI surveillance
Target prevalence in this cancer
- 2001COMS: brachytherapy equals enucleation for medium tumours
- 2004Gene-expression classes 1 and 2 predict metastasis (Onken, Harbour)
- 2009GNAQ mutations discovered (Van Raamsdonk); GNA11 in 2010
- 2010BAP1 loss drives metastasis (Harbour, Science)
- 2021Tebentafusp improves overall survival (NEJM)
- 2022Tebentafusp approved
FDA January 2022; EMA April 2022.
- 2023Percutaneous hepatic perfusion (Hepzato) approved
Open problems
- Half of patients metastasise with no adjuvant therapy despite accurate prediction.
- Tebentafusp only for HLA-A*02:01 (about 45% of white patients, fewer elsewhere) and gives few objective responses despite OS benefit.
- Liver-tropic metastasis biology poorly understood.
- Vision-preserving local therapy still causes radiation retinopathy.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy, Ipilimumab, Nivolumab
- via Proton therapy, Nivolumab
- American Society for Radiation OncologyArlington, VA, USvia Brachytherapy, Proton therapy
- via Ipilimumab, Nivolumab
- European Society for Radiotherapy and OncologyBrussels, BEvia Brachytherapy, Proton therapy
- via Ipilimumab, Nivolumab
- via Brachytherapy, Proton therapy
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Proton therapy, Nivolumab
- Aarhus University HospitalAarhus, DKvia Proton therapy
- Apollo Hospitals (Apollo Cancer Centres)Chennai, INvia Proton therapy
- via Proton therapy
- Cancer Institute (WIA), AdyarChennai, INvia Brachytherapy
- via Proton therapy
- Centre Antoine LacassagneNice, FRvia Proton therapy
- Centre Oscar LambretLille, FRvia Brachytherapy
- Chang Gung Memorial HospitalTaoyuan, TWvia Proton therapy
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Proton therapy
- Cleveland Clinic Abu DhabiAbu Dhabi, AEvia Proton therapy
- via Proton therapy
- Dharmais National Cancer CenterJakarta, IDvia Brachytherapy
- Erasmus MC Cancer InstituteRotterdam, NLvia Proton therapy
- via Brachytherapy
- German Hodgkin Study GroupCologne, DEvia Nivolumab
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia Brachytherapy
- Hacettepe University Cancer InstituteAnkara, TRvia Brachytherapy
- Ho Chi Minh City Oncology HospitalHo Chi Minh City, VNvia Brachytherapy
- Hokkaido University HospitalSapporo, JPvia Proton therapy
- Institut BergoniéBordeaux, FRvia Brachytherapy
- Institut National d'Oncologie, RabatRabat, MAvia Brachytherapy
- Institut Salah AzaïezTunis, TNvia Brachytherapy
- Institute of Oncology LjubljanaLjubljana, SIvia Brachytherapy
- via Brachytherapy
- Instituto Nacional de Cancerología (Mexico)Mexico City, MXvia Brachytherapy
- via Brachytherapy
- via Brachytherapy
- via Brachytherapy
- Istanbul University Institute of OncologyIstanbul, TRvia Brachytherapy
- Kenyatta National HospitalNairobi, KEvia Brachytherapy
- via Proton therapy
- Koo Foundation Sun Yat-Sen Cancer CenterTaipei, TWvia Brachytherapy
- Korle Bu Teaching HospitalAccra, GHvia Brachytherapy
- Kyoto University HospitalKyoto, JPvia Nivolumab
- Lagos University Teaching HospitalLagos, NGvia Brachytherapy
- via Nivolumab
- Leiden University Medical CenterLeiden, NLvia Proton therapy
- via Brachytherapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- National Cancer Center KoreaGoyang, KRvia Proton therapy
- National Cancer Centre SingaporeSingapore, SGvia Proton therapy
- National Institute of Oncology, HungaryBudapest, HUvia Brachytherapy
- National Taiwan University HospitalTaipei, TWvia Proton therapy
- via Proton therapy
- via Proton therapy
- Ocean Road Cancer InstituteDar es Salaam, TZvia Brachytherapy
- via Proton therapy
- via Tebentafusp
- via Brachytherapy
- via Proton therapy
- Royal Adelaide HospitalAdelaide, AUvia Proton therapy
- Ruijin Hospital, Shanghai Jiao Tong UniversityShanghai, CNvia Proton therapy
- via Proton therapy
- Shizuoka Cancer CenterNagaizumi, Shizuoka, JPvia Proton therapy
- via Proton therapy
- Sunnybrook Odette Cancer CentreToronto, ON, CAvia Brachytherapy
- SWOG Cancer Research NetworkPortland, OR, USvia Nivolumab
- via Proton therapy
- Uganda Cancer InstituteKampala, UGvia Brachytherapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Proton therapy
- via Proton therapy
- UZ Leuven / Leuven Cancer InstituteLeuven, BEvia Proton therapy
- Velindre Cancer CentreCardiff, GBvia Brachytherapy
- Zhejiang Cancer HospitalHangzhou, CNvia Proton therapy
Questions to ask
topQuestions to ask your oncologist about Uveal melanoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example GNAQ / GNA11 mutations, BAP1 loss and monosomy 3, SF3B1, EIF1AX, Gene-expression profileand PRAME, HLA-A*02:01), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Choroidal melanoma, Ciliary body melanoma, Iris melanoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Primary tumour
- For my situation (primary tumour), which of the standard options do you recommend and why?Why: Guideline options include: Plaque brachytherapy (I-125 or Ru-106) or proton beam radiotherapy for most; enucleation for large tumours; prognostic biopsy for GEP/chromosome 3.
Surveillance
- For my situation (surveillance), which of the standard options do you recommend and why?Why: Guideline options include: Risk-adapted liver imaging (MRI/ultrasound) every 6-12 months for high-risk GEP class 2 / monosomy 3; no proven adjuvant therapy.
Metastatic, HLA-A*02:01-positive
- For my situation (metastatic, hla-a*02:01-positive), which of the standard options do you recommend and why?Why: Guideline options include: Tebentafusp weekly (OS 21.7 vs 16.0 months vs investigator's choice); manage cytokine release and rash.
- Am I a candidate for Tebentafusp, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, HLA-A*02:01-negative or liver-dominant
- For my situation (metastatic, hla-a*02:01-negative or liver-dominant), which of the standard options do you recommend and why?Why: Guideline options include: Percutaneous hepatic perfusion with melphalan (FOCUS trial; approved 2023), radioembolisation, hepatic resection; ipilimumab-nivolumab (~15% response); clinical trials (darovasertib-crizotinib).
- Am I a candidate for Melphalan (including hepatic delivery system), Ipilimumab, Nivolumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Tebentafusp, Percutaneous hepatic perfusion (chemosaturation), Brenetafusp?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Half of patients metastasise with no adjuvant therapy despite accurate prediction”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Tebentafusp only for HLA-A*02:01 (about 45% of white patients, fewer elsewhere) and gives few objective responses despite OS benefit”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
11targets
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2pathways
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3collections
1Latest papers
topQuery for this cancer: (TITLE:"Uveal melanoma" OR ABSTRACT:"Uveal melanoma" OR TITLE:"Ocular melanoma" OR ABSTRACT:"Ocular melanoma" OR TITLE:"Choroidal melanoma" OR ABSTRACT:"Choroidal melanoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Uveal melanoma, not a curated reading list.
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