The first 60 days: 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. Below, week by week, is what OnCo's record of Uveal melanoma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Primary tumour.
- RadiologistNamed in the standard of care for: Surveillance.
- SurgeonNamed in the standard of care for: Metastatic, HLA-A*02:01-negative or liver-dominant.
- Medical oncologistNamed in the standard of care for: Primary tumour, Surveillance, Metastatic, HLA-A*02:01-positive, Metastatic, HLA-A*02:01-negative or liver-dominant.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Primary tumour, Metastatic, HLA-A*02:01-negative or liver-dominant.
- Transplant and cell therapy teamNamed in the standard of care for: Metastatic, HLA-A*02:01-positive, Metastatic, HLA-A*02:01-negative or liver-dominant.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Plaque brachytherapy (I-125 or Ru-106) or proton beam radiotherapy for most; enucleation for large tumours; prognostic biopsy for GEP/chromosome 3.
- 2.Metastatic, HLA-A*02:01-positiveNCCN category Category 1, ESMO-MCBS 4, NCCN Guidelines: Uveal Melanoma
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).
Risk-adapted liver imaging (MRI/ultrasound) every 6-12 months for high-risk GEP class 2 / monosomy 3; no proven adjuvant therapy.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Choroidal melanoma, Ciliary body melanoma, Iris melanoma.
- Is germline (inherited) genetic testing recommended for me or my family?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?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?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?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?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?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?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, Darovasertib?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?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?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?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?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Phase 3 Randomized, Masked, Controlled Trial to Evaluate Efficacy and Safety of Belzupacap Sarotalocan (AU-011) Treatment Compared to Sham Control in Subjects With Primary Indeterminate Lesions or Small Choroidal MelanomaPhase 3 · active · NCT06007690A Phase 3 Randomized, Masked, Controlled Trial to Evaluate Efficacy and Safety of Belzupacap Sarotalocan (AU-011) Treatment Compared to Sham Control in Subjects With Primary Indeterminate Lesions or Small Choroidal Melanoma
- An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular MelanomaPhase 3 · active · NCT05022901An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma
- Neoadjuvant Darovasertib in Primary Uveal MelanomaPhase 3 · recruiting · NCT07015190A Randomized, Phase 3, Open-label Study of Neoadjuvant Darovasertib in Subjects With Primary Non-metastatic Uveal Melanoma (OptimUM-10)
- Study of Adjuvant Darovasertib and Crizotinib in Participants With Primary Non-metastatic Uveal MelanomaPhase 3 · recruiting · NCT07804186A Randomized, Phase 3, Open-label Study of Adjuvant Darovasertib and Crizotinib in Participants With Primary Non-metastatic Uveal Melanoma
- A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult PPhase 2/3 · recruiting · NCT06581406A Randomized, Phase 2/3, Open-Label Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab Versus Ipilimumab in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Uveal melanoma: the full pageA 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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- HLA-A*02:01 restriction: Some T-cell-receptor drugs only work in people with a particular immune 'tissue type'.
- Seed and soil hypothesis of metastasis (Paget): Stephen Paget asked in 1889 why breast cancer spread to some organs more than blood flow could explain, and answered that a travelling cancer cell (the seed) grows only where the organ (the soil) suits it.
- Cytokine release syndrome (CRS): A flood of inflammatory signals when immune cells are activated en masse, causing fever, low blood pressure, and sometimes organ failure.
- Rare cancers: Rare cancers are those with fewer than about 6 new cases per 100,000 people per year.
Every term links to the glossary.