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13 standard-of-care settings across 7 lines and 2 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.
| Line | All comers | BRAF |
|---|---|---|
| Screening, prevention and diagnosis | 1 | · |
| Early / localised | 3 | · |
| Locally advanced | 2 | · |
| Advanced, first line | 3 | · |
| Second line | · | 1 |
| Special situations | 1 | · |
| Other settings | 2 | · |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Screening and diagnosis | Dermoscopy, total-body photography for high-risk patients, excisional biopsy with Breslow thickness and ulceration reported; AI decision support emerging. | 32 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Stage II-III | Adjuvant pembrolizumab/nivolumab; neoadjuvant IO for resectable stage III. | NCCN Guidelines: Melanoma: Cutaneous | 98 | |
| All comers | Stage I-II primary | Wide local excision with margins by thickness (1-2 cm); sentinel lymph node biopsy from ~0.8 mm Breslow or with ulceration; nodal ultrasound surveillance rather than completion dissection if positive (MSLT-II). | NCCN · Category 1 for SLNB thresholds | 83 | |
| All comers | Stage IIB-IIC (thick or ulcerated, node-negative) | Adjuvant pembrolizumab or nivolumab for one year (KEYNOTE-716, CheckMate 76K); discuss modest absolute benefit and irAE risk; ctDNA-guided trials. | NCCN · 2AESMO-MCBS · A | 98 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Resectable stage III (macroscopic nodes) | Neoadjuvant ipilimumab + nivolumab (two cycles) then surgery with response-adapted adjuvant therapy (NADINA), or neoadjuvant pembrolizumab (SWOG S1801); alternative adjuvant-only PD-1 or, if BRAF-mutant, dabrafenib-trametinib. | NCCN · Preferred (neoadjuvant IO) | 87 | |
| All comers | Stage III after surgery (adjuvant) | Nivolumab or pembrolizumab for one year; dabrafenib-trametinib for BRAF V600 (COMBI-AD, 10-year RFS 48%); relatlimab adds nothing (RELATIVITY-098). | NCCN · 1ESMO-MCBS · A | 92 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Metastatic first line | Nivolumab-ipilimumab or nivolumab-relatlimab; BRAF/MEK if rapid control needed. | NCCN Guidelines: Melanoma: Cutaneous | 97 | |
| All comers | Unresectable or metastatic, first line | Nivolumab + ipilimumab (highest long-term survival; ~59% grade 3-4 events) or nivolumab + relatlimab (Opdualag; ~21%) or anti-PD-1 alone; for BRAF-mutant disease, immunotherapy first (DREAMseq) unless rapid control is needed. | NCCN · 1 (preferred)ESMO-MCBS · 4-5 | 95 | |
| All comers | Metastatic uveal melanoma (HLA-A*02:01-positive) | Tebentafusp (OS benefit, IMCgp100-202); liver-directed therapy for hepatic-dominant disease; ipilimumab-nivolumab has modest activity. | NCCN · 1 | 78 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| BRAF | BRAF V600-mutant, after immunotherapy or needing rapid response | BRAF + MEK doublet: encorafenib-binimetinib, dabrafenib-trametinib, or vemurafenib-cobimetinib; triplet with atezolizumab is approved but little used. | NCCN · 1 | 97 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Brain metastases | Nivolumab + ipilimumab for asymptomatic disease (~50% intracranial response, CheckMate 204); stereotactic radiosurgery; BRAF/MEK for symptomatic BRAF-mutant disease. | 98 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | After PD-1 | Lifileucel, RP1 + nivolumab, ipilimumab-based, trials; tebentafusp (uveal). | NCCN Guidelines: Melanoma: Cutaneous | 74 | |
| All comers | After anti-PD-1 failure | Lifileucel TIL therapy (accelerated approval 2024), RP1 oncolytic virus + nivolumab (2026), ipilimumab-based rechallenge, brenetafusp trials; clinical trials strongly encouraged. | NCCN · 2A | 68 |
In BRAF-mutant melanoma, start with immunotherapy and keep the targeted pills in reserve; the reverse order costs lives.
Treat before surgery, look at the removed tumour, and only continue treatment if the response was incomplete.
When checkpoint blockade fails in melanoma, harvesting and expanding the patient's own tumour-reactive T cells still works in a third of patients.
LAG-3 blockers helped in measurable melanoma with one drug pairing, but failed as adjuvant therapy and with a different PD-1 partner.
Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.