Advanced melanoma: the decisions you may face
6 treatment settings, 5 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
First line, fit patient
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).
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
Opdualag combines relatlimab, the first drug targeting the LAG-3 immune brake, with nivolumab for melanoma.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
- Tests Nivolumab, IpilimumabUntreated advanced melanoma: nivolumab + ipilimumab vs nivolumab vs ipilimumab
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.
- 10-year OS 43% vs 37% vs 19%.
Progression-free survival (co-primary) (months): Nivolumab + ipilimumab 11.5 vs Nivolumab 6.9 vs Ipilimumab 2.9 · HR 0.42 · source - Tests Nivolumab, Relatlimab + nivolumabUntreated unresectable or metastatic melanoma: nivolumab + relatlimab (fixed dose) vs nivolumab
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.
- PFS HR 0.75; median OS 51.0 vs 34.1 months.
- Tests Ipilimumab, PembrolizumabAdvanced melanoma, ≤1 prior systemic therapy: pembrolizumab (two schedules) vs ipilimumab
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.
- 10-year OS 34.0% vs 23.6%.
- Tests Nivolumab, IpilimumabUntreated BRAF V600 metastatic melanoma: nivolumab + ipilimumab then dabrafenib + trametinib at progression, vs the reverse sequence
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.
- 2-year OS 71.8% vs 51.5%.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Nivolumab, Ipilimumab, Relatlimab + nivolumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in CheckMate 067 and RELATIVITY-047, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Nivolumab or Ipilimumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (first line, fit patient), which of the standard options do you recommend and why?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?Why: 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?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
BRAF V600-mutant, after immunotherapy or when rapid control is needed
Dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib.
Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.
Encorafenib is a BRAF inhibitor that, with cetuximab and chemotherapy, became first-line standard for BRAF-mutant colorectal cancer in 2026.
Binimetinib is the MEK inhibitor partnered with encorafenib; blocking the next step in the same relay stops the tumour rerouting around the BRAF block.
- Tests Encorafenib, BinimetinibAdvanced BRAF V600 melanoma: encorafenib + binimetinib vs vemurafenib vs encorafenib
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.
- PFS 14.9 vs 7.3 months (HR 0.54); median OS 33.6 months.
Progression-free survival (months): Encorafenib + binimetinib 14.9 vs Vemurafenib 7.3 · HR 0.54 · source - Tests Dabrafenib + trametinibUntreated unresectable or metastatic BRAF V600E or V600K melanoma: dabrafenib plus trametinib versus dabrafenib plus placebo
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.
- Median progression-free survival 11.0 vs 8.8 months; median overall survival 25.1 vs 18.7 months (HR 0.71); pooled COMBI-d/v 5-year overall survival 34%.
Progression-free survival (months): Dabrafenib + trametinib 11 (n=211) vs Dabrafenib + placebo 8.8 (n=212) · HR 0.67 · source - Untreated unresectable or metastatic BRAF V600-mutant melanoma: vemurafenib plus cobimetinib versus vemurafenib plus placebo
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.
- Median progression-free survival 12.3 vs 7.2 months (HR 0.58); median overall survival 22.3 vs 17.4 months (HR 0.70).
Progression-free survival (months): Vemurafenib + cobimetinib 12.3 (n=247) vs Vemurafenib + placebo 7.2 (n=248) · HR 0.58 · source
- Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Between Dabrafenib + trametinib, Encorafenib and Binimetinib, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in COLUMBUS and COMBI-d, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (braf v600-mutant, after immunotherapy or when rapid control is needed), which of the standard options do you recommend and why?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?Why: 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?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Brain metastases
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.
A single very high dose, or a few doses, aimed at a small brain or spine target with millimetre precision, replacing whole-brain radiotherapy for most brain metastases.
- One to five sessions
- Spares healthy brain
- Treats targets surgery cannot reach
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
- Melanoma with untreated brain metastases: nivolumab plus ipilimumab, asymptomatic cohort and a smaller symptomatic cohort
Intracranial clinical benefit 57% and complete response 26% in the asymptomatic cohort.
Intracranial clinical benefit rate (asymptomatic cohort) (%): Nivolumab + ipilimumab 57 (n=94) · source
- Limited to small targets
- Radiation necrosis in a minority
- Needs precise imaging and immobilisation
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS), Nivolumab and Ipilimumab, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in CheckMate 204, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Nivolumab or Ipilimumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (brain metastases), which of the standard options do you recommend and why?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?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 204 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
After PD-1 failure
Lifileucel TIL therapy (C-144-01); RP1 with nivolumab; ipilimumab-based combinations; clinical trials; imatinib for KIT-mutant tumours.
Lifileucel was the first approved TIL therapy: the patient's own tumour-fighting immune cells are expanded to billions and given back.
Immune cells that have already found their way into the tumour are harvested, grown to billions, and returned.
- Naturally polyclonal against the patient's own neoantigens
- Works in solid tumours
Vusolimogene oderparepvec is an engineered herpes virus injected into melanoma tumours, approved in August 2026 with nivolumab after immunotherapy failure.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
The drug that started the targeted therapy era in 2001, turning chronic myeloid leukaemia into a manageable condition with near-normal life expectancy.
- Tests Lifileucel, TIL therapyAdvanced melanoma progressing after anti-PD-1 (and BRAF/MEK if applicable): single infusion of lifileucel TIL
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.
- ORR 31.4%; median DOR 36.5 months (5-year analysis).
- Requires resectable tumour and 3-4 week manufacturing
- IL-2 toxicity
- Single-centre logistics
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Take with a meal and a large glass of water.
- Between Lifileucel, TIL therapy, Vusolimogene oderparepvec and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in C-144-01, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Ipilimumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (after pd-1 failure), which of the standard options do you recommend and why?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?Why: 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?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Treatment duration
Stop anti-PD-1 therapy after two years or after a confirmed complete response; most remissions hold off treatment (KEYNOTE-006).
This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.
- Advanced melanoma, ≤1 prior systemic therapy: pembrolizumab (two schedules) vs ipilimumab
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.
- 10-year OS 34.0% vs 23.6%.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Which specific treatments are you proposing for this setting, and what are the alternatives?Why: The standard of care here is described in words rather than named products; ask for the names.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in KEYNOTE-006, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (treatment duration), which of the standard options do you recommend and why?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?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Oligometastatic disease
Surgery or radiosurgery for isolated metastases alongside systemic therapy; isolated limb perfusion for limb-confined disease.
A single very high dose, or a few doses, aimed at a small brain or spine target with millimetre precision, replacing whole-brain radiotherapy for most brain metastases.
- One to five sessions
- Spares healthy brain
- Treats targets surgery cannot reach
Isolating the blood supply of an arm or leg so that chemotherapy doses 15-20 times higher than the body could tolerate can be circulated through it, to save limbs with melanoma or sarcoma that would otherwise be amputated.
- Limb salvage in otherwise unresectable sarcoma
- High complete response in melanoma in-transit disease
- Minimal systemic toxicity when leak is controlled
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Limited to small targets
- Radiation necrosis in a minority
- Needs precise imaging and immobilisation
- Major operation; regional toxicity (Wieberdink grade)
- TNF-α not approved in the US
- Displaced in melanoma by systemic immunotherapy
- Between Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS) and Isolated limb perfusion and infusion, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (oligometastatic disease), which of the standard options do you recommend and why?Why: Guideline options include: Surgery or radiosurgery for isolated metastases alongside systemic therapy; isolated limb perfusion for limb-confined disease.
Add these to your appointment list, or take the full question set for this cancer.