NADINA
Trial question
What is the role of neoadjuvant nivolumab plus ipilimumab in patients with resectable, macroscopic stage III melanoma?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
35.0% female
65.0% male
N = 423
423 patients (147 female, 276 male).
Inclusion criteria: patients with resectable, macroscopic stage III melanoma.
Key exclusion criteria: distantly metastasized melanoma; uveal/ocular or mucosal melanoma; in-transit metastases only; prior radiotherapy; autoimmune disease or a history of syndrome that required systemic corticosteroids or immunosuppressive therapy.
Interventions
N=212 neoadjuvant ipilimumab plus nivolumab (2 cycles of ipilimumab at a dose of 80 mg plus nivolumab at a dose of 240 mg every 3 weeks followed by surgery).
N=211 adjuvant nivolumab (surgery followed by 12 cycles of nivolumab every 4 weeks).
Primary outcome
Event-free survival at 12 months
83.7%
57.2%
83.7 %
62.8 %
41.9 %
20.9 %
0.0 %
Neoadjuvant ipilimumab plus
nivolumab
Adjuvant
nivolumab
Significant
increase ▲
NNT = 3
Significant increase in event-free survival at 12 months (83.7% vs. 57.2%; HR 3.13, 99% CI 1.52 to 6.67).
Secondary outcomes
Significant increase in event-free survival at 12 months in patients with melanoma with BRAF V600E or V600K mutation (83.5% vs. 52.2%; HR 3.45, 99% CI 1.27 to 9.09).
No significant difference in event-free survival at 12 months in patients with BRAF wild-type melanoma (83.9% vs. 62.4%; HR 2.86, 99% CI 0.97 to 8.33).
Safety outcomes
No significant difference in adverse events.
Conclusion
In patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab was superior to adjuvant nivolumab with respect to a event-free survival at 12 months.
Reference
Christian U Blank, Minke W Lucas, Richard A Scolyer et al. Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma. N Engl J Med. 2024 Nov 7;391(18):1696-1708.
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