Two courses of neoadjuvant ipilimumab/nivolumab highly improve event free survival (EFS) in patients with macroscopic stage 3 melanoma, compared to standard adjuvant nivolumab, according to results of the phase 3 NADINA trial.

The standard management of resectable, macroscopic stage 3 melanoma is currently surgery, which can be followed by adjuvant systemic therapy. Despite adjuvant systemic treatment, a substantial proportion of patients have a recurrence within the first few years after surgery. Additionally, none of the approved adjuvant immunotherapies have shown a significant overall survival (OS) benefit despite long-term follow-up^1,2.

Previously, it was shown that neoadjuvant ipilimumab/nivolumab results in higher pathological response and EFS compared to neoadjuvant PD-1 blockade³. The NADINA trial (NCT04949113) is the first randomized, phase 3 trial to compare neoadjuvant ipilimumab/nivolumab with current standard care of adjuvant anti-PD-1. Professor Christan Blank, MD, of Antoni van Leeuwenhoek, in the Netherlands, presented the results⁴.

In NADINA, 423 patients were 1:1 randomly assigned to surgery followed by 12 courses of nivolumab (480 mg q4w) or 2 courses ipilimumab (80 mg) and nivolumab (240 mg) followed by surgery. Participants who had a major pathologic response did not receive any additional treatment; participants without a major pathologic response received 11 courses of nivolumab (480 mg) or dabrafinib/trametinib in case of BRAF^V600E/k) .

EFS rate at 12 months after randomization was 83.7% with neoadjuvant treatment versus 57.2% with adjuvant treatment (HR 0.32 [99.9% CI 0.15-0.66]; P<0.0001). EFS benefit of neoadjuvant treatment was observed in all prespecified subgroups (e.g. BRAF wildtype vs BRAF^V600E/K).

Of neoadjuvant treated patients, many had a major pathologic response and did not receive any adjuvant treatment. The EFS rate at 12 months in patients who achieved a major pathologic response was 95%.

“Neoadjuvant combination of ipilimumab plus nivolumab results in a highly statistically significant EFS benefit as compared to standard of care adjuvant PD-1 blockade in patients with resectable, macroscopic stage 3 melanoma. Nearly 60% of patients in the neoadjuvant arm needed only 6 weeks of treatment,” concluded Professor Blank.

Medical writing support was provided by Marten Dooper, PhD.
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