Melanoma: lines of therapy

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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	·

Screening, prevention and diagnosis

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.	Dermoscopy, total-body photography & AI skin analysisBreslow thicknessUlceration (melanoma)		32

Early / localised

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Stage II-III	Adjuvant pembrolizumab/nivolumab; neoadjuvant IO for resectable stage III.	PembrolizumabNivolumabSentinel lymph node biopsy	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).	Sentinel lymph node biopsyMSLT-IIUltrasound	NCCN · Category 1 for SLNB thresholds	79
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.	KEYNOTE-716PembrolizumabNivolumab	NCCN · 2AESMO-MCBS · A	98

Locally advanced

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.	NADINASWOG S1801COMBI-ADMajor pathological response (MPR)	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).	COMBI-ADDabrafenib + trametinibRELATIVITY-098	NCCN · 1ESMO-MCBS · A	84

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Metastatic first line	Nivolumab-ipilimumab or nivolumab-relatlimab; BRAF/MEK if rapid control needed.	CheckMate 067Relatlimab + nivolumabEncorafenib	NCCN Guidelines: Melanoma: Cutaneous	89
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.	CheckMate 067RELATIVITY-047KEYNOTE-006DREAMseq (ECOG-ACRIN EA6134)Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)	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.	TebentafuspIMCgp100-202HLA-A*02:01 restriction	NCCN · 1	93

Second line

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.	COLUMBUSEncorafenibBinimetinibVemurafenibCobimetinibBRAF inhibitor + MEK inhibitor	NCCN · 1	88

Special situations

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.	NivolumabIpilimumabSBRT / SABR (stereotactic radiotherapy)		86

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	After PD-1	Lifileucel, RP1 + nivolumab, ipilimumab-based, trials; tebentafusp (uveal).	LifileucelVusolimogene oderparepvecTebentafusp	NCCN Guidelines: Melanoma: Cutaneous	81
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.	LifileucelC-144-01Vusolimogene oderparepvecPRISM-MEL-301Brenetafusp	NCCN · 2A	68

Sequence and caution pairings

SequenceStandard of care

Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)

In BRAF-mutant melanoma, start with immunotherapy and keep the targeted pills in reserve; the reverse order costs lives.

SequenceStandard of care

Neoadjuvant immunotherapy → response-adapted adjuvant

Treat before surgery, look at the removed tumour, and only continue treatment if the response was incomplete.

SequenceStandard of care

PD-1 failure → TIL therapy

When checkpoint blockade fails in melanoma, harvesting and expanding the patient's own tumour-reactive T cells still works in a third of patients.

CautionApproved

Caution: LAG-3 blockade outside active disease

LAG-3 blockers helped in measurable melanoma with one drug pairing, but failed as adjuvant therapy and with a different PD-1 partner.

Regimens in the library

Nivolumab + ipilimumab (melanoma)Pembrolizumab monotherapy Dabrafenib + trametinib Nivolumab + relatlimab

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.