Background
Phase III double-blind RCT (CheckMate 76K), N=790 completely resected stage IIB/IIC cutaneous melanoma (AJCC 8th ed; T3b-T4b N0 M0). Stratified by T-stage and region. Enrolled 2020-2022 across 130 sites.
Interventions and follow up
Arm A: Nivolumab 480 mg IV q4wk × up to 13 cycles (~1 year)
Arm B: Placebo × up to 13 cycles
Primary endpoint: Recurrence-free survival (RFS)
mFollow up: 15.8 months
Arm B: Placebo × up to 13 cycles
Primary endpoint: Recurrence-free survival (RFS)
mFollow up: 15.8 months
Results
12-month RFS: 89.0% vs 79.4%, HR 0.58, 95% CI 0.40-0.84, P=.0004
DMFS: HR 0.47, 95% CI 0.29-0.76 (exploratory)
OS: immature at primary analysis
DMFS: HR 0.47, 95% CI 0.29-0.76 (exploratory)
OS: immature at primary analysis
Adverse events
Grade ≥3 AEs: 16.9% vs 6.9%
Immune-mediated AEs any grade: 27.4% vs 4.4%; Grade ≥3 5.1% vs 0.7%
Most common immune AEs: thyroid disorders 17.6%, rash/skin reactions 6.0%, arthritis 3.3%
Discontinuation due to AE: 9.9% vs 1.5%
Immune-mediated AEs any grade: 27.4% vs 4.4%; Grade ≥3 5.1% vs 0.7%
Most common immune AEs: thyroid disorders 17.6%, rash/skin reactions 6.0%, arthritis 3.3%
Discontinuation due to AE: 9.9% vs 1.5%
Conclusions
Adjuvant nivolumab significantly reduced recurrence risk vs placebo in resected stage IIB/IIC melanoma (HR 0.58, P=.0004), confirming adjuvant PD-1 inhibition as effective in high-risk node-negative melanoma. The numerically lower HR vs pembrolizumab in KEYNOTE-716 (0.65) likely reflects follow-up and population differences rather than true efficacy differences.
Key Limitations
Short median follow-up (15.8 months); OS immature, requiring maturation to assess whether RFS benefit translates to OS. DMFS exploratory (HR 0.47), not co-primary. No validated predictive biomarker to select stage IIB/IIC patients. RFS benefit must be weighed against toxicity (immune AEs ~27%, discontinuation ~10%) and favorable baseline prognosis. No head-to-head with pembrolizumab (KEYNOTE-716).
Clinical Context
FDA approved nivolumab (Opdivo) for adjuvant stage IIB/IIC resected melanoma (July 2022) based on CheckMate 76K. Together with pembrolizumab (KEYNOTE-716), nivolumab is a standard adjuvant option for high-risk node-negative (stage IIB/IIC) melanoma; ESMO lists both as preferred options. These approvals expanded adjuvant immunotherapy from stage III (established 2017) to stage IIB/IIC (approved 2021-2022). The higher DMFS HR (0.47) vs pembrolizumab's (0.64) likely reflects maturation differences and should not be cross-compared.