The first 60 days: BRAF V600-mutant melanoma
BRAF V600-mutant melanoma has a single faulty switch that drives it to grow, and two pills, a BRAF inhibitor with a MEK inhibitor, can shut that switch off and shrink the cancer within weeks. Immunotherapy is usually given first because its effect lasts longer, and the pills are kept for later or given for a year after surgery to prevent relapse. Below, week by week, is what OnCo's record of BRAF V600-mutant 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: Triplet therapy.
- Medical oncologistNamed in the standard of care for: Advanced, first line, Advanced, after immunotherapy, Resected stage III, Brain metastases and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Brain metastases.
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.
A year of adjuvant dabrafenib-trametinib (COMBI-AD) or of adjuvant nivolumab or pembrolizumab; neoadjuvant immunotherapy for macroscopic nodal disease.
Nivolumab plus ipilimumab or nivolumab plus relatlimab first (DREAMseq); dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib first only when a rapid response is needed.
BRAF plus MEK inhibitor doublet (COMBI-d, coBRIM, COLUMBUS); encorafenib-binimetinib has the longest median survival and least fever of the three.
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.
Atezolizumab with vemurafenib-cobimetinib (IMspire150) is approved but little used because it lengthened progression-free survival without a clear survival gain.
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 by sequencing or immunohistochemistry, Lactate dehydrogenase, Number of metastatic sites, NRAS, MEK1 and BRAF splice variants at resistance, Circulating tumour DNA BRAF V600 for response monitoring), 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 BRAF V600E-mutant melanoma, BRAF V600K-mutant melanoma, BRAF non-V600 or class 2 and 3 mutations.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and 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?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?Trial populations differ from individual patients; ask how closely you match.
Advanced, after immunotherapy
- For my situation (advanced, after immunotherapy), which of the standard options do you recommend and 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?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?Trial populations differ from individual patients; ask how closely you match.
Resected stage III
- For my situation (resected stage iii), which of the standard options do you recommend and 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?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?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 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?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.
Triplet therapy
- For my situation (triplet therapy), which of the standard options do you recommend and 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?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2), Naporafenib, Belvarafenib in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic NRAS-Mutant Melanoma, Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma?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 “Responses to targeted therapy are almost universal but most are not durable, and resistance through MAPK reactivation has no approved answer”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether a short targeted-therapy induction before immunotherapy helps has not been settled in a phase 3 trial”. 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 Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic MelanomaPhase 3 · active · NCT04657991A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS PLACEBO PLUS PEMBROLIZUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE METASTATIC OR UNRESECTABLE LOCALLY ADVANCED 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]
- Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.Phase 3 · active · NCT05270044Adjuvant Encorafenib & Binimetinib vs. Placebo in Fully Resected Stage IIB/C BRAF V600E/K Mutated Melanoma: a Randomized Triple-blind Phase III Study in Collaboration With the EORTC Melanoma Group
- Belvarafenib in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic NRAS-Mutant MelanomaPhase 2 · recruiting · NCT07449754A Phase 2, Multicenter, Single-Arm Study of Belvarafenib (HM95573) in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic NRAS-Mutant Melanoma
- Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic MelanomaPhase 2 · active · NCT04417621A Randomized, Open-label, Multi-arm, Two-part, Phase II Study to Assess Efficacy and Safety of Multiple LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic BRAFV600 or NRAS Mutant 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.
- BRAF V600-mutant melanoma: the full pageBRAF V600-mutant melanoma has a single faulty switch that drives it to grow, and two pills, a BRAF inhibitor with a MEK inhibitor, can shut that switch off and shrink the cancer within weeks. Immunotherapy is usually given first because its effect lasts longer, and the pills are kept for later or given for a year after surgery to prevent relapse.
- 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.
- BRAF V600E mutation: A single spelling change in the BRAF gene that jams a growth switch permanently on.
Every term links to the glossary.