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Advanced melanoma has spread beyond what surgery can remove, and it is the cancer in which immunotherapy first proved it could cure some people: about half of those given nivolumab with ipilimumab are alive ten years later. If immunotherapy fails, options include a cell therapy grown from the patient's own immune cells, a virus injected into the tumour, and targeted pills for BRAF-mutant disease.
Until 2011 advanced melanoma was treated with dacarbazine, which shrank about one tumour in ten, or high-dose interleukin-2, which produced rare durable remissions at great toxicity; median survival was six to nine months. Ipilimumab (2010) was the first drug to lengthen survival, from 6.4 to 10.1 months, and produced a plateau with about one in five patients alive long term. PD-1 blockade then transformed the disease: in KEYNOTE-006 pembrolizumab beat ipilimumab with ten-year survival of 34.0 against 23.6 percent, and in CheckMate 067 nivolumab plus ipilimumab, nivolumab and ipilimumab gave ten-year survival of 43, 37 and 19 percent. RELATIVITY-047 (2022) added the LAG-3 antibody relatlimab to nivolumab and lengthened progression-free survival from 4.6 to 10.1 months with about a third of the severe toxicity of the ipilimumab combination.
First-line choice therefore lies between nivolumab-ipilimumab (deepest and longest data, most toxic), nivolumab-relatlimab (less toxic, no proven survival advantage over nivolumab alone) and anti-PD-1 monotherapy for frail patients, with treatment stopped after two years or after a confirmed complete response (KEYNOTE-006). BRAF-mutant patients are treated with immunotherapy first and BRAF-MEK inhibitors second on the DREAMseq result, unless rapid control is needed. Asymptomatic brain metastases respond to nivolumab-ipilimumab (intracranial clinical benefit 57 percent in CheckMate 204) and are treated with drugs first, with radiosurgery for symptomatic or progressing lesions; the details are on the brain metastases page.
After PD-1 failure, tumour-infiltrating lymphocyte therapy produced responses in 31 percent of heavily pretreated patients in C-144-01, and the Dutch randomised trial found progression-free survival of 7.2 against 3.1 months for TIL versus ipilimumab; lifileucel became the first approved cell therapy for a solid tumour in February 2024. The oncolytic virus RP1 (vusolimogene oderparepvec) with nivolumab was approved in 2026 for PD-1-refractory disease, and ipilimumab-based combinations, clinical trials and, for the rare KIT-mutant tumour, imatinib remain options. Fianlimab plus cemiplimab, the PRAME-directed bispecific brenetafusp, the PRAME TCR-T cell therapy IMA203, faecal microbiota transplantation to reverse PD-1 resistance and first-line lifileucel with pembrolizumab (TILVANCE-301) are in phase 3 or pivotal trials.
Roughly one in ten melanomas presents with or progresses to unresectable or metastatic disease; before 2011 median survival was under a year, and about half of patients treated with the nivolumab and ipilimumab combination are now alive at ten years.
Each skin cancer comes from a different cell layer: melanocytes and basal cells at the base of the epidermis, keratinocytes above them, Merkel cells and blood vessels in the dermis; depth of invasion decides the risk.
Same organ: Melanoma, Basal cell carcinoma, Cutaneous squamous cell carcinoma, Merkel cell carcinoma, Kaposi sarcoma, Skin cancer (all types), BRAF V600-mutant melanoma, Stage III melanoma (after surgery), Stage IIB and IIC melanoma, Mucosal melanoma, Acral melanoma, Advanced cutaneous squamous cell carcinoma, Locally advanced and metastatic basal cell carcinoma, Bowen's disease (squamous cell carcinoma in situ), Dermatofibrosarcoma protuberans
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).
Dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib.
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.
Lifileucel TIL therapy (C-144-01); RP1 with nivolumab; ipilimumab-based combinations; clinical trials; imatinib for KIT-mutant tumours.
Stop anti-PD-1 therapy after two years or after a confirmed complete response; most remissions hold off treatment (KEYNOTE-006).
Surgery or radiosurgery for isolated metastases alongside systemic therapy; isolated limb perfusion for limb-confined disease.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Take with a meal and a large glass of water.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
See all on the product pages:BinimetinibDabrafenib + trametinibEncorafenibImatinibIpilimumabNivolumabPembrolizumabRelatlimab + nivolumab·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with Advanced melanoma, then print the one-page appointment sheet with room for the answers.
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.