BRAF V600-mutant melanoma: the decisions you may face
5 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.
Advanced, first line
Nivolumab plus ipilimumab or nivolumab plus relatlimab first (DREAMseq); dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib first only when a rapid response is needed.
Opdualag combines relatlimab, the first drug targeting the LAG-3 immune brake, with nivolumab for melanoma.
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.
Vemurafenib was the first BRAF inhibitor (2011); it shrank melanomas in weeks and proved that a single mutation could be drugged in a solid tumour.
Cobimetinib is the MEK partner for vemurafenib, and the first drug approved for histiocytic neoplasms.
- Tests Dabrafenib + trametinibUntreated 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%.
- Untreated 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
- 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.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Arthralgia | 53% | - |
| Photosensitivity | 33% | - |
| Cutaneous squamous cell carcinoma / keratoacanthoma · BRIM-3 vemurafenib arm | 24% | - |
- Severe photosensitivity: sun protection.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Relatlimab + nivolumab, Dabrafenib + trametinib, Encorafenib 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 DREAMseq (ECOG-ACRIN EA6134) and CheckMate 067, 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 Vemurafenib 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 (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Nivolumab plus ipilimumab or nivolumab plus relatlimab first (DREAMseq); dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib first only when a rapid response is needed.
- Am I a candidate for Relatlimab + nivolumab, Dabrafenib + trametinib, Encorafenib 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 DREAMseq (ECOG-ACRIN EA6134) and CheckMate 067 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.
Advanced, after immunotherapy
BRAF plus MEK inhibitor doublet (COMBI-d, coBRIM, COLUMBUS); encorafenib-binimetinib has the longest median survival and least fever of the three.
Dabrafenib (Tafinlar) is a capsule that switches off the faulty BRAF protein driving some melanomas, lung, thyroid and other cancers. It is almost always paired with trametinib.
Trametinib (Mekinist) blocks MEK, the protein one step below BRAF in the growth-signal chain. Paired with dabrafenib it treats BRAF-mutant melanoma, lung, thyroid and other cancers, including brain tumours in children.
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 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 - 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
- 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 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 COMBI-d and coBRIM, 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 (advanced, after immunotherapy), which of the standard options do you recommend and why?Why: Guideline options include: BRAF plus MEK inhibitor doublet (COMBI-d, coBRIM, COLUMBUS); encorafenib-binimetinib has the longest median survival and least fever of the three.
- Am I a candidate for Dabrafenib, Trametinib, Encorafenib 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 COMBI-d and coBRIM 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.
Resected stage III
A year of adjuvant dabrafenib-trametinib (COMBI-AD) or of adjuvant nivolumab or pembrolizumab; neoadjuvant immunotherapy for macroscopic nodal disease.
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.
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.
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 Dabrafenib + trametinibResected stage III BRAF V600-mutant melanoma: adjuvant dabrafenib + trametinib 1 year vs 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.
- 10-year RFS 48% vs 32%; DMFS 63% vs 48%.
- Tests NivolumabResectable macroscopic stage III melanoma: two cycles neoadjuvant ipilimumab + nivolumab then surgery (adjuvant only if incomplete response) vs surgery then 12 cycles adjuvant nivolumab
12-month EFS 83.7% vs 57.2%; HR 0.32.
Event-free survival at 12 months (%): Neoadjuvant ipilimumab + nivolumab 83.7 vs Adjuvant nivolumab 57.2 · HR 0.32 · source
- Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
| 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+ |
|---|---|---|
| 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 Dabrafenib + trametinib, Nivolumab and Pembrolizumab, 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 COMBI-AD and NADINA, 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 Pembrolizumab 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 (resected stage iii), which of the standard options do you recommend and why?Why: Guideline options include: A year of adjuvant dabrafenib-trametinib (COMBI-AD) or of adjuvant nivolumab or pembrolizumab; neoadjuvant immunotherapy for macroscopic nodal disease.
- Am I a candidate for Dabrafenib + trametinib, Nivolumab, Pembrolizumab, 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 COMBI-AD and NADINA 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 for asymptomatic lesions (CheckMate 204); dabrafenib-trametinib when a fast intracranial response is needed (COMBI-MB); radiosurgery for symptomatic or progressing lesions.
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.
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
- 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
- Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
- Limited to small targets
- Radiation necrosis in a minority
- Needs precise imaging and immobilisation
- Between Dabrafenib + trametinib and Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS), 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.
- 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 for asymptomatic lesions (CheckMate 204); dabrafenib-trametinib when a fast intracranial response is needed (COMBI-MB); radiosurgery for symptomatic or progressing lesions.
- Am I a candidate for Dabrafenib + trametinib, 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.
Triplet therapy
Atezolizumab with vemurafenib-cobimetinib (IMspire150) is approved but little used because it lengthened progression-free survival without a clear survival gain.
A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery.
Vemurafenib was the first BRAF inhibitor (2011); it shrank melanomas in weeks and proved that a single mutation could be drugged in a solid tumour.
Cobimetinib is the MEK partner for vemurafenib, and the first drug approved for histiocytic neoplasms.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (immune-mediated) · Monotherapy pooled | 3% | 0.8% |
| Hepatitis (immune-mediated) · Monotherapy pooled | 1.8% | 0.7% |
| Colitis (immune-mediated) · Monotherapy pooled | 1% | 0.5% |
| Hypothyroidism (immune-mediated) · Monotherapy pooled | 4.9% | 0.2% |
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+ |
|---|---|---|
| Arthralgia | 53% | - |
| Photosensitivity | 33% | - |
| Cutaneous squamous cell carcinoma / keratoacanthoma · BRIM-3 vemurafenib arm | 24% | - |
- Severe photosensitivity: sun protection.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Atezolizumab, Vemurafenib and Cobimetinib, 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.
- Which side effects of Atezolizumab or Vemurafenib 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.
- For my situation (triplet therapy), which of the standard options do you recommend and why?Why: Guideline options include: Atezolizumab with vemurafenib-cobimetinib (IMspire150) is approved but little used because it lengthened progression-free survival without a clear survival gain.
- Am I a candidate for Atezolizumab, Vemurafenib, Cobimetinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.