Advanced melanoma (unresectable stage III and stage IV): lines of therapy

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6 standard-of-care settings across 4 lines and 3 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	Fit
Advanced, first line	·	·	1
Second line	·	1	·
Special situations	2	·	·
Other settings	2	·	·

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
Fit	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).	CheckMate 067RELATIVITY-047KEYNOTE-006DREAMseq (ECOG-ACRIN EA6134)NivolumabIpilimumabRelatlimab + nivolumabPembrolizumab	NCCN Guidelines: Melanoma: Cutaneous	98

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
BRAF	BRAF V600-mutant, after immunotherapy or when rapid control is needed	Dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib.	BRAF V600-mutant melanomaDabrafenib + trametinibEncorafenibBinimetinibCOLUMBUSCOMBI-dcoBRIM	NCCN Guidelines: Melanoma: Cutaneous	89

Special situations

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	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.	CheckMate 204Brain metastases (secondary brain tumours)Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)NivolumabIpilimumab	NCCN Guidelines: Melanoma: Cutaneous	86
All comers	Oligometastatic disease	Surgery or radiosurgery for isolated metastases alongside systemic therapy; isolated limb perfusion for limb-confined disease.	Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Isolated limb perfusion and infusion	NCCN Guidelines: Melanoma: Cutaneous	76

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	After PD-1 failure	Lifileucel TIL therapy (C-144-01); RP1 with nivolumab; ipilimumab-based combinations; clinical trials; imatinib for KIT-mutant tumours.	LifileucelC-144-01TIL therapyVusolimogene oderparepvecIpilimumabImatinib	NCCN Guidelines: Melanoma: Cutaneous	82
All comers	Treatment duration	Stop anti-PD-1 therapy after two years or after a confirmed complete response; most remissions hold off treatment (KEYNOTE-006).	KEYNOTE-006Fixed-duration vs continuous therapy	NCCN Guidelines: Melanoma: Cutaneous	95

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.