First-line systemic therapy
- For unresectable or metastatic disease, recommended treatment options include checkpoint immunotherapy, BRAF-targeted therapy for patients with BRAF-mutated disease, or clinical trial.
- Checkpoint immunotherapy options include anti-programmed cell death protein-1 (PD-1) monotherapy with pembrolizumab (category 2A), nivolumab (category 1), or nivolumab/ipilimumab combination therapy (category 2A).
- Single-agent ipilimumab monotherapy is no longer recommended by the National Comprehensive Cancer Network (NCCN) as a first-line therapy option: results from the CheckMate 067 phase 3 trial demonstrated better outcomes with anti-PD-1 monotherapy or nivolumab/ipilimumab combination therapy vs ipilimumab alone.
- In BRAF-mutant metastatic disease, first-line targeted therapies include BRAF/MEK inhibitor combination therapy with dabrafenib/trametinib or vemurafenib/cobimetinib, or single-agent BRAF inhibitor therapy with vemurafenib or dabrafenib. All are category 1 recommendations based on results from phase 3 trials...