The first 60 days: Advanced melanoma (unresectable stage III and stage IV)
Advanced melanoma has spread beyond what surgery can remove, and it is the cancer in which immunotherapy first proved it could cure some people: about half of those given nivolumab with ipilimumab are alive ten years later. If immunotherapy fails, options include a cell therapy grown from the patient's own immune cells, a virus injected into the tumour, and targeted pills for BRAF-mutant disease. Below, week by week, is what OnCo's record of Advanced melanoma (unresectable stage III and stage IV) 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: Oligometastatic disease.
- SurgeonNamed in the standard of care for: Oligometastatic disease.
- Medical oncologistNamed in the standard of care for: First line, fit patient, BRAF V600-mutant, after immunotherapy or when rapid control is needed, Brain metastases, After PD-1 failure and 2 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Brain metastases, Oligometastatic disease.
- Transplant and cell therapy teamNamed in the standard of care for: After PD-1 failure.
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.
Nivolumab plus ipilimumab (CheckMate 067) or nivolumab plus relatlimab (RELATIVITY-047); anti-PD-1 monotherapy where toxicity must be minimised (KEYNOTE-006). Immunotherapy first even when BRAF-mutant (DREAMseq).
- 2.BRAF V600-mutant, after immunotherapy or when rapid control is neededNCCN Guidelines: Melanoma: Cutaneous
Dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib.
Nivolumab plus ipilimumab first for asymptomatic lesions (CheckMate 204); radiosurgery for symptomatic or progressing lesions; dabrafenib-trametinib in BRAF-mutant disease needing fast control. See the brain metastases page.
Lifileucel TIL therapy (C-144-01); RP1 with nivolumab; ipilimumab-based combinations; clinical trials; imatinib for KIT-mutant tumours.
Stop anti-PD-1 therapy after two years or after a confirmed complete response; most remissions hold off treatment (KEYNOTE-006).
Surgery or radiosurgery for isolated metastases alongside systemic therapy; isolated limb perfusion for limb-confined disease.
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 BRAF V600 mutation, Lactate dehydrogenase, PD-L1 expression, Tumour mutational burden and interferon-gamma signature, NRAS and KIT mutations), 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 Unresectable stage III, Stage IV M1a to M1c, Stage IV M1d.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
First line, fit patient
- For my situation (first line, fit patient), which of the standard options do you recommend and why?Guideline options include: Nivolumab plus ipilimumab (CheckMate 067) or nivolumab plus relatlimab (RELATIVITY-047); anti-PD-1 monotherapy where toxicity must be minimised (KEYNOTE-006). Immunotherapy first even when BRAF-mutant (DREAMseq).
- Am I a candidate for Nivolumab, Ipilimumab, Relatlimab + nivolumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 067 and RELATIVITY-047 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
BRAF V600-mutant, after immunotherapy or when rapid control is needed
- For my situation (braf v600-mutant, after immunotherapy or when rapid control is needed), which of the standard options do you recommend and why?Guideline options include: Dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib.
- Am I a candidate for Dabrafenib + trametinib, Encorafenib, Binimetinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of COLUMBUS and COMBI-d apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Brain metastases
- For my situation (brain metastases), which of the standard options do you recommend and why?Guideline options include: Nivolumab plus ipilimumab first for asymptomatic lesions (CheckMate 204); radiosurgery for symptomatic or progressing lesions; dabrafenib-trametinib in BRAF-mutant disease needing fast control. See the brain metastases page.
- Am I a candidate for Nivolumab, Ipilimumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 204 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
After PD-1 failure
- For my situation (after pd-1 failure), which of the standard options do you recommend and why?Guideline options include: Lifileucel TIL therapy (C-144-01); RP1 with nivolumab; ipilimumab-based combinations; clinical trials; imatinib for KIT-mutant tumours.
- Am I a candidate for Lifileucel, Vusolimogene oderparepvec, Ipilimumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of C-144-01 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Treatment duration
- For my situation (treatment duration), which of the standard options do you recommend and why?Guideline options include: Stop anti-PD-1 therapy after two years or after a confirmed complete response; most remissions hold off treatment (KEYNOTE-006).
- How do the results of KEYNOTE-006 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Oligometastatic disease
- For my situation (oligometastatic disease), which of the standard options do you recommend and why?Guideline options include: Surgery or radiosurgery for isolated metastases alongside systemic therapy; isolated limb perfusion for limb-confined disease.
Any stage
- Are there clinical trials I could join, for example of Fianlimab + cemiplimab phase 3 (first-line melanoma), Fianlimab, PRISM-MEL-301, Brenetafusp?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 “About four in ten patients never respond to PD-1 blockade and no biomarker reliably identifies them”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Who needs the ipilimumab component and its toxicity, and whether relatlimab can replace it, has not been settled”. 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 Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination (FDC) in Previously Untreated Metastatic or Unresectable MelanomaPhase 3 · active · NCT05625399A Phase 3, Randomized, Open-label, Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination Versus Intravenous Nivolumab + Relatlimab Fixed-dose Combination in Participants With Previously Untreated Metastatic or Unresectable Melanoma
- A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)Phase 3 · active · NCT06346067A Randomized, Open-label Phase III Study in Patients With Previously Treated Unresectable or Metastatic NRAS Mutant Cutaneous Melanoma Comparing the Combination of Naporafenib + Trametinib to Physician's Choice of Therapy (Dacarbazine, Temozolomide or Trametinib Monotherapy) With a Dose Optimization lead-in [SEACRAFT-2]
- Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant MelanomaPhase 3 · recruiting · NCT06008106Efficacy and Safety of Tunlametinib Capsules Versus Combination Chemotherapy of Investigator's Choice in Advanced NRAS-mutant Melanoma Patients Who Had Previously Received Immunotherapy
- IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013 / KN-D18)Phase 3 · active · NCT05155254An Open-label, Randomized, Phase 3 Clinical Trial of IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Patients With Previously Untreated, Unresectable, or Metastatic (Advanced) Melanoma (IO102-IO103-013 / MK3475-D18)
- PRISM-MEL-301Phase 3 · recruiting · NCT06112314Untreated HLA-A*02:01-positive advanced cutaneous melanoma: brenetafusp + nivolumab vs nivolumab-based regimens
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Advanced melanoma (unresectable stage III and stage IV): the full pageAdvanced melanoma has spread beyond what surgery can remove, and it is the cancer in which immunotherapy first proved it could cure some people: about half of those given nivolumab with ipilimumab are alive ten years later. If immunotherapy fails, options include a cell therapy grown from the patient's own immune cells, a virus injected into the tumour, and targeted pills for BRAF-mutant 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.
- Fixed-duration vs continuous therapy: Whether a drug is taken for a set period (say 12 months) and then stopped even though it is still working, or continued indefinitely until it fails.
- Immune-related adverse events (irAEs): Immune-related adverse events (irAEs) are the autoimmune side effects of checkpoint inhibitors: colitis, thyroid problems, rash, hepatitis, pneumonitis.
- Brain metastases (intracranial disease): Tumour deposits that have travelled to the brain from a cancer elsewhere, ten times more common than cancers that start in the brain, mostly from lung, breast, melanoma and kidney cancer.
Every term links to the glossary.