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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| 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). | not mapped |
| BRAF V600-mutant, after immunotherapy or when rapid control is needed | Dabrafenib-trametinib, encorafenib-binimetinib or vemurafenib-cobimetinib. | not mapped |
| 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. | not mapped |
| After PD-1 failure | Lifileucel TIL therapy (C-144-01); RP1 with nivolumab; ipilimumab-based combinations; clinical trials; imatinib for KIT-mutant tumours. | not mapped |
| Treatment duration | Stop anti-PD-1 therapy after two years or after a confirmed complete response; most remissions hold off treatment (KEYNOTE-006). | not mapped |
| Oligometastatic disease | Surgery or radiosurgery for isolated metastases alongside systemic therapy; isolated limb perfusion for limb-confined disease. | not mapped |