Melanoma: guideline history

Anchored to: FDA approval of nivolumab with ipilimumab, September 2015 (accelerated) and CheckMate 067 overall-survival data

• addedUnresectable or metastatic, first line: Nivolumab plus ipilimumab, and single-agent anti-PD-1, as preferred first-line regimens; ipilimumab alone moves to other options.

Anchored to: FDA approval of adjuvant dabrafenib plus trametinib, April 2018 (COMBI-AD), following adjuvant nivolumab (December 2017)

• addedAdjuvant, stage III, BRAF V600-mutant: Dabrafenib plus trametinib for one year as an alternative to anti-PD-1 adjuvant therapy.

Anchored to: FDA approvals of adjuvant pembrolizumab for stage IIB-IIC (December 2021, KEYNOTE-716) and nivolumab plus relatlimab (March 2022, RELATIVITY-047)

• addedAdjuvant, stage IIB-IIC: Pembrolizumab for one year after resection of stage IIB or IIC melanoma.
• addedUnresectable or metastatic, first line: Nivolumab plus relatlimab as a first-line option with less toxicity than nivolumab plus ipilimumab.

Anchored to: DREAMseq publication (JCO, January 2023)

• recategorisedUnresectable or metastatic, BRAF V600-mutant, first line: Immunotherapy stated as preferred over BRAF/MEK inhibition in the first line for BRAF-mutant disease, based on DREAMseq.either sequence acceptable → checkpoint inhibitor first, BRAF/MEK on progression

Anchored to: FDA accelerated approval of lifileucel (February 2024) and NADINA publication (NEJM, June 2024)

• addedUnresectable or metastatic, after anti-PD-1: Lifileucel (TIL therapy) after progression on anti-PD-1 and, if BRAF-mutant, BRAF/MEK inhibition.
• addedResectable stage III, neoadjuvant: Neoadjuvant nivolumab plus ipilimumab followed by response-adapted adjuvant therapy, based on NADINA and SWOG S1801.