Adjuvant Immunotherapy in Melanoma

Stage-Specific Indications

The American Society of Clinical Oncology recommends pembrolizumab for 52 weeks as a strongly recommended option for Stage IIB-C melanoma, based on the KEYNOTE-716 trial demonstrating substantial recurrence-free survival benefit 1
The American Society of Clinical Oncology recommends nivolumab for 52 weeks as a recommended option for Stage IIB-C melanoma, based on the CheckMate 76K trial showing similar efficacy and toxicity profiles to pembrolizumab 1
For Stage IIIA-D melanoma with BRAF V600E/K mutation, the National Comprehensive Cancer Network recommends three equivalent first-line options: nivolumab for 52 weeks, pembrolizumab for 52 weeks, or dabrafenib plus trametinib for 52 weeks, with high-quality evidence supporting their use 2, 1
The National Comprehensive Cancer Network recommends BRAF mutation testing for all Stage III-IV melanoma to determine eligibility for dabrafenib plus trametinib, with testing identifying V600E or V600K mutations specifically 2, 1

The CheckMate 238 trial demonstrated nivolumab's superiority over ipilimumab, with 12-month recurrence-free survival of 70.5% vs 60.8%, HR 0.65, P<0.001 4
The KEYNOTE-054 trial showed pembrolizumab's efficacy, with 12-month recurrence-free survival of 75% vs 61% for placebo, HR 0.57, P<0.001 4
Nivolumab demonstrated superior recurrence-free survival and significantly lower toxicity compared to high-dose ipilimumab, with grade 3-4 adverse events occurring in 14.4% of patients on nivolumab vs 45.9% on ipilimumab 4

The National Comprehensive Cancer Network recommends nivolumab 3 mg/kg IV every 2 weeks or 480 mg IV every 4 weeks for 52 weeks, and pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks for 52 weeks 2
Dabrafenib plus trametinib is recommended at dabrafenib 150 mg PO twice daily plus trametinib 2 mg PO once daily for 52 weeks 2

BRAF mutation testing is mandatory for all Stage III-IV melanoma to determine eligibility for dabrafenib plus trametinib, with testing identifying V600E or V600K mutations specifically 2, 1
PD-L1 testing is not required for adjuvant therapy selection, as subgroup analyses from CheckMate 238 and KEYNOTE-054 showed benefit regardless of PD-L1 expression status 7

Grade 3-4 adverse events occurred in 25-41% of patients across adjuvant trials with anti-PD-1 agents and BRAF/MEK inhibitors, which is substantially lower than historical adjuvant options 5, 6
Any-grade immune-related adverse events affect up to 90% of patients on ipilimumab, and treatment discontinuation due to adverse events occurred in 9.7% of patients on nivolumab vs 42.6% on ipilimumab 8, 4